Apoptosis In Liver Cancer Cells Research Articles

The essential oils isolated from the fruit of Ficus carica induced reactive oxygen species and apoptosis of human liver cancer cells

The essential oils isolated from the fruit of Ficus carica induced reactive oxygen species and apoptosis of human liver cancer cells

A Study on Curcumol Influencing Proliferation and Apoptosis of Hepatocellular Carcinoma Cells through DJ-1/PTEN/PI3K/AKT Pathway.

Objective To study the mechanism of curcumol affecting the proliferation and apoptosis of liver cancer cells through the DJ-1/PTEN/PI3K/AKT pathway. Method HepG2 cells were cultured in vitro, treated with curcumol at concentrations of 10, 30, and 100 μg/mL, and DMSO was used as a control. The levels of cell proliferation and apoptosis were measured by CCK-8 and flow cytometry, respectively. RT-PCR and western blot were used to detect PTEN, p-AKT, DJ-1, and PI3K gene and protein expression changes. Result (1) Compared with the DMSO blank control group, the proliferation level of liver cancer cells in the 10 μg/mL curcumol group decreased, and the proportion of apoptosis increased (p <0.05). (2) Compared with the blank control group and the 10 and 30 μg/mL concentration groups, the proliferation level of liver cancer cells in the 100 μg/mL curcumol group was significantly reduced, and the proportion of cell apoptosis was significantly increased (p < 0.05). (3) Curcumol can significantly increase the expression of PTEN gene and protein in liver cancer cells and reduce the expression of DJ-1 and PI3K genes and protein in liver cancer cells (p < 0.05). Conclusion Curcumol can regulate DJ-1, PTEN, PI3K, and AKT signal transduction pathways, inhibit cell proliferation, and cause a significant increase in the proportion of cell apoptosis, and the pharmacodynamic effect of curcumol is dependent on the time and dose of action.

Abrine Elicits Liver Carcinoma Immunity and Enhances Antitumor Efficacy of Immune Checkpoint Blockade by Modulating PD-L1 Signaling.

Background Liver cancer is the most malignant type of human malignancies. In recent years, immune therapy that targets the immune check points such as programmed cell death ligand 1 (PD-L1) has achieve great success. Abrine is the dominant alkaloid in Abrus cantoniensis and Abrus precatorius Linn. that exhibited anticancer effect. This work is aimed at studying the effects of abrine in immunity of liver cancer. Methods Cell viability, proliferation, and migration were assessed by CCK-8, Edu, and Transwell assay. Cell apoptosis was checked by flow cytometry. Tumor growth was determined by an in vivo xenograft model. Quantitative real-time PCR assay was conducted to evaluate the levels of KAT5 and PD-L1. T cells and liver cancer cells were cocultured in a Transwell system, and the levels of PD-L1 and PD-1 was checked by flow cytometry. The interaction between KAT5 and PD-L1 was determined by ChIP assay. Results Abrine treatment suppressed liver tumor growth both in vitro and in vivo and simultaneously decreased the level of PD-L1 and KAT5. In the coculture system, treatment with abrine inhibited proliferation and activity of cocultured T cell. KAT5 epigenetically elevated recruitment of H3k27ac and RNA polymerase II to PD-L1 promoter region. Ectopic expression of KAT5 and PD-L1 reversed the function of abrine on tumor growth and T cell function. Conclusion Abrine modulated growth and apoptosis of liver cancer cells and regulated proliferation and activation of T cells through the KAT5/PD-L1 axis.

Purified PTEN-Long Induces Liver Cancer Cells to Undergo Autophagy and Apoptosis.

BackgroundPTEN-Long is a translational variant of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). This tumor suppressor is frequently lost or mutated and even it has been shown as the determinant in several human tumors. Therefore, we will determine the significant roles of PTEN-Long in the development of liver cancer.MethodsIn the present study, we characterized the antitumor effects of PTEN-Long and PTEN in proliferation, migration of HepG2 cells, apoptosis and autophagy in liver cancer cells. To extends, we have also measured the effects of purified PTEN and PTEN-Long in the above index of HepG2 cells.ResultsPTEN and PTEN-Long were ectopic-expressed in HepG2 cells, and their phenotypic effects were recorded. As expected, there was less expression of PTEN-Long and PTEN in liver cancer samples than in paired normal tissues. Ectopic expression of PTEN-Long or PTEN significantly decreased the proliferation and migration of HepG2 cells and increased apoptosis. PTEN ectopic-expression increased the number of GFP-/RFP+-LC3 puncta and levels of beclin-1 and LC3BII/LC3BI, suggesting autophagy induction. Purified PTEN-Long freely entered cells, decreased proliferation, and increased autophagy and apoptosis, while purified PTEN did not.ConclusionsOur results identify an antitumor function of purified PTEN-Long and suggest its potential utility for liver cancer treatment.

Influence of 6-shogaol potentiated on 5-fluorouracil treatment of liver cancer by promoting apoptosis and cell cycle arrest by regulating AKT/mTOR/MRP1 signalling.

Currently, chemoresistance seriously attenuates the curative outcome of liver cancer. The purpose of our work was to investigate the influence of 6-shogaol on the inhibition of 5-fluorouracil (5-FU) in liver cancer. The cell viability of cancer cells was determined by MTT assay. Liver cancer cell apoptosis and the cell cycle were examined utilizing flow cytometry. Moreover, qRT-PCR and western blotting was used to analyse the mRNA and protein expression levels, respectively. Immunohistochemistry assays were used to examine multidrug resistance protein 1 (MRP1) expression in tumour tissues. In liver cancer cells, we found that 6-shogaol-5-FU combination treatment inhibited cell viability, facilitated G0/G1 cell cycle arrest, and accelerated apoptosis compared with 6-shogaol or 5-FU treatment alone. In cancer cells cotreated with 6-shogaol and 5-FU, AKT/mTOR pathway- and cell cycle-related protein expression levels were inhibited, and MRP1 expression was downregulated. AKT activation or MRP1 increase reversed the influence of combination treatment on liver cancer cell viability, apoptosis and cell cycle arrest. The inhibition of AKT activation to the anticancer effect of 6-shogaol-5-FU could be reversed by MRP1 silencing. Moreover, our results showed that 6-shogaol-5-FU combination treatment notably inhibited tumour growth in vivo. In summary, our data demonstrated that 6-shogaol contributed to the curative outcome of 5-FU in liver cancer by inhibiting the AKT/mTOR/MRP1 signalling pathway.

Deciphering the Molecular Mechanism of Red Raspberry in Apoptosis of Liver Cancer Cells.

Red raspberry contains a variety of bioactive ingredients and has high edible and medicinal value. Red raspberry extractions (RREs) have strong antioxidant capacity and anticancer ability in vivo and in vitro. This study was to explore the specific mechanism of RREs inhibiting the proliferation of liver cancer HepG2 cells and provide a theoretical basis for the prevention and treatment of liver cancer by RREs. HepG2 cells were cultured in vitro, and MTT assay was adopted to detect the effect of RREs on HepG2 cell activity. Colony formation assay was applied to detect the growth and proliferation of cells, cell apoptosis was detected by flow cytometry, and dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay was adopted to detect the effect of RREs on the production of reactive oxygen species (ROS) in cells. The effect of RREs on cell mitochondrial membrane potential was evaluated by mitochondrial membrane potential assay kit with JC-1 (JC-1 assay), and western blot was used to detect the expression of apoptosis-related proteins (B-cell lymphoma-2 (Bcl-2), Bcl-2-associated x (Bax), and Caspase-3), thus investigating the effect of RREs on the molecular mechanism of HepG2 cell apoptosis. The results showed that RREs could inhibit the proliferation activity of HepG2 cells and promote their apoptosis in a concentration-dependent manner. The level of ROS in HepG2 cells interfered by RREs increased markedly, while the cell mitochondrial membrane potential decreased sharply. As the concentration of HepG2 increased, the mitochondrial membrane potential reduced steeply. Western blot results showed that the expression of apoptosis-related protein Bcl-2 in the RREs treatment group dropped, but the expression of Bax and Caspase-3 rose. In summary, RREs could inhibit the proliferation of liver cancer HepG2 cells and promote their apoptosis. This inhibition might be executed by inducing HepG2 cells to produce ROS, a decrease in Bcl-2/Bax protein ratio, and an obvious reduction in mitochondrial membrane potential.

Mechanism of Phellodendron and Anemarrhena Drug Pair on the Treatment of Liver Cancer Based on Network Pharmacology and Bioinformatics.

BackgroundThis study aims to explore the key targets and signaling pathways of the traditional Chinese medicine Phellodendron and Anemarrhena drug pair (PADP) for the treatment of liver cancer.MethodsFirstly, bioinformatics technology was used to analyze GSE62232 gene chip to obtain the differential genes of liver cancer. A network pharmacology technology was used to find the active components of PADP and their targets. Secondly, the differential genes were imported into STRING database to draw a PPI network, and network topology structure map combined with Cytoscape software. And the R language was used to identify differential gene targets and pathways through GO and KEGG pathway enrichment analysis. In addition, AutoDock Vina was used for molecular docking of core targets and core compounds. Moreover, GEPIA online analysis tool was used to perform survival analysis of the core target genes. Finally, RT-PCR was used to verify the changes of key target genes. CCK−8 assay was performed to detect cell proliferation. Flow cytometry was performed to detect the cell cycle and apoptotic. Transwell invasion assay was performed to detect cell invasion.ResultsFirstly, a total of 21,654 genes were obtained. After screening, 1019 differential genes were obtained, including 614 down-regulated genes and 405 up-regulated genes. Furthermore, after screening by ADME standards, 52 active ingredients were obtained, of which 37 were Phellodendron and 15 were Anemarrhena. And a total of 36 differential genes have been identified, including 13 up-regulated genes and 23 down-regulated genes. Moreover, through enrichment analysis, we found that PADP may treat liver cancer through multiple channels and multiple pathways including the p53 signaling pathway, IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway and so on. Secondly, the molecular docking results showed that there was certain affinity between the core compounds and core target genes. In addition, GEPIA online analysis showed that ESR1, AR, CCNB1, CDK1, AKR1C3 and CCNA2 might become potential target genes for the survival and prognosis of PADP for the treatment of liver cancer. Finally, it was found that PADP could up regulate genes ESR1 and AR, down regulate genes CCNB1, CDK1, AKR1C3, and CCNA2. PADP could promote the apoptosis of liver cancer cells, shorten the cell cycle, and inhibit the proliferation and invasion of liver cancer cells.ConclusionPADP may treat liver cancer through multiple targets, multiple channels, and multiple pathways, thereby suppressing cancer cells and improving the living quality of patients.

Zhenzhu Xiaoji Decoction Induces Autophagy and Apoptosis Cell Death in Liver Cancer Cells through AKT/mTOR and JAK2/STAT3 Signaling Pathway.

Background Liver cancer is one of the most common digestive tumors. The prescription Zhenzhu Xiaoji decoction (ZZXJD) has a certain effect on the growth and survival of primary liver cancer. Object: This article aimed to explore the effect and molecular mechanism of ZZXJD on liver cancer SMMC-7721 cells. Method The research groups were divided into the model group, ZZXJD group, and cisplatin group. SMMC-7721 cells were treated with different concentrations of ZZXJD-medicated serum for 24 h and 48 h. The cell viability was measured with CCK8 assay, and cell morphology was observed by fluorescence microscope and transmission electron microscope (TEM). Western blot, RT-PCR, and gene chip were used to determine the protein expression level and gene expression level of cells and tumor tissues. Results ZZXJD inhibited the proliferation activity of SMMC-7721 cells in a concentration- and time-dependent manner. The morphological changes of the cell showed apoptosis and autophagy. The gene expression of protein kinase B (AKT), mammalian target of rapamycin (mTOR), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3(STAT3) were downregulated compared with the model group(p < 0.05). The nude mice experiments confirmed that ZZXJD inhibited the growth of tumors in tumor-bearing mice, and the effect increased with the increase of concentration. Conclusion ZZXJD induced autophagy and apoptosis of liver cancer cells via inhibiting AKT/mTOR signaling pathway and JAK2/STAT3 signaling pathway, thereby affecting the growth and survival of liver cancer cells.

Exploring the Effect of Polyphyllin I on Hepatitis B Virus-related Liver Cancer through Network Pharmacology and in vitro Experiments.

To investigate the effect of Polyphyllin I (PPI) on HBV-related liver cancer through network pharmacology and in vitro experiments, and to explore its mechanism of action. Use bioinformatics software to predict the active ingredient target of PPI and the disease target of liver cancer, and perform active ingredient-disease target analysis. The results of network pharmacology through molecular docking and in vitro experiments can be further verified. The HepG2 receptor cells (HepG2. 2. 15) were transfected with HBV plasmid for observation, with the human liver cancer HepG2 being used as the control. Bioinformatics analysis found that PPI had a total of 161 protein targets, and the predicted target and liver cancer targets were combined to obtain 13 intersection targets. The results of molecular docking demonstrated that PPI had a good affinity with STAT3, PTP1B, IL2, and BCL2L1. The results of the in vitro experiments indicated that the PPI inhibited cell proliferation and metastasis in a concentration-dependent manner (P<0.01). Compared with the vehicle group, the PPI group of 1.5, 3, and 6 μmol/L can promote the apoptosis of liver cancer to different degrees (P<0.01). The present study revealed the mechanism of PPI against liver cancer through network pharmacology and in vitro experiments. Its mechanism of action is related to the inhibition of PPI on the proliferation of HBV-related liver cancer through promoting the apoptosis of liver cancer cells. Additionally, in vitro experiments have also verified that PPI can promote the apoptosis of HepG2 and HepG2.2.15 cells.

Dehydrocrenatidine Induces Liver Cancer Cell Apoptosis by Suppressing JNK-Mediated Signaling

Liver cancer is a leading cause of death worldwide. Despite advancement in therapeutic interventions, liver cancer is associated with poor prognosis because of highly lethal characteristics and high recurrence rate. In the present study, the anticancer potential of a plant-based alkaloid namely dehydrocrenatidine has been evaluated in human liver cancer cells. The study findings revealed that dehydrocrenatidine reduced cancer cell viability by arresting cell cycle at G2/M phase and activating mitochondria-mediated and death receptor-mediated apoptotic pathways. Specifically, dehydrocrenatidine significantly increased the expression of extrinsic pathway components (FAS, DR5, FADD, and TRADD) as well as intrinsic pathway components (Bax and Bim L/S) in liver cancer cells. In addition, dehydrocrenatidine significantly increased the cleavage and activation of PARP and caspases 3, 8, and 9. The analysis of upstream signaling pathways revealed that dehydrocrenatidine induced caspase-mediated apoptosis by suppressing the phosphorylation of JNK1/2. Taken together, the study identifies dehydrocrenatidine as a potent anticancer agent that can be use clinically to inhibit the proliferation of human liver cancer cells.

−808 nm-activated Ca2+ doped up-conversion nanoparticles that release no inducing liver cancer cell (HepG2) apoptosis

A near-infrared (NIR) light-triggered release method for nitric oxide (NO) was developed utilizing core/shell NaYF4: Tm/Yb/Ca@NaGdF4: Nd/Yb up-conversion nanoparticles (UCNPs) bearing a mesoporous silica (mSiO2) shell loaded with the NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP). To avoid overheating in biological samples, Nd3+ was chosen as a sensitizer, Yb3+ ions as the bridging sensitizer, and Tm3+ ions as UV-emissive activator while co-doping with Ca2+ was done to enhance the luminescence of the activator Tm3+. NO release from SNAP was triggered by an NIR-UV up-conversion process, initiated by 808 nm light absorbed by the Nd3+ ions. NO release was confirmed by the Griess method. Under 808 nm irradiation, the viability of the liver cancer cell line HepG2 significantly decreased with increasing UCNPs@mSiO2-SNAP concentration. For a UCNPs@mSiO2-SNAP concentration of 200 μg ml−1, the cell survival probability was 47%. These results demonstrate that UCNPs@mSiO2-SNAP can induce the release of apoptosis-inducing NO by NIR irradiation.

The Apoptosis of Liver Cancer Cells Promoted by Curcumin/TPP-CZL Nanomicelles With Mitochondrial Targeting Function.

The mitochondrion is one of the most important cellular organelles, and many drugs work by acting on mitochondria. Curcumin (Cur)-induced apoptosis of HepG2 in liver cancer cells is closely related to the function of inhibiting mitochondria. However, the mitochondrion-targeting curcumin delivery system was rarely been reported. It is important to develop a high-efficiency mitochondrion-targeting curcumin vector that can deliver curcumin into mitochondria directly. Here, a special mitochondrion-targeting delivery system based on triphenylphosphine bromide (TPP)-chitosan-g-poly-(N-3-carbobenzyloxy-l-lysine) (CZL) with TPP functional on the surface is designed to perform highly efficient mitochondria-targeting delivery for effective liver cancer cell killing in vitro. The TEM images showed that the nanomicelles were spherical; the results of fluorescence test showed that TPP-CZL nanomicelles could promote the cellular uptake of drugs and finally targeted to the mitochondria. The results of cell survival rate and Hoechst staining showed that curcumin/TPP-CZL nanomicelles could promote the apoptosis of liver cancer cells. Curcumin/TPP-CZL nanomicelles could significantly reduce the mitochondrial membrane potential, increase the expression of pro apoptotic protein Bcl-2, and reduce the expression of antiapoptotic Bax protein, and these results were significantly better than curcumin/CZL nanomicelles and curcumin. It is a potential drug delivery system with high efficiency to target mitochondria of liver cancer cells.

Exploring the Study of miR-1301 Inhibiting the Proliferation and Migration of Squamous Cell Carcinoma YD-38 Cells through PI3K/AKT Pathway under Deep Learning Medical Images.

With the rapid development and application of deep learning medical image recognition, natural language processing, and other fields, at the same time, deep learning has become the most popular research direction in the field of image processing and recognition. Through deep learning medical image recognition technology, it is of great significance to explore the research of miR-1301. The purpose of this article is to use an improved CNN neural network model algorithm combined to contrast the experimental groups and use deep learning medical imaging technology to study the mechanism by which miR-1301 inhibits the proliferation of carcinoma YD-38 cells through the PI3K/AKT pathway. This paper studies the method of image recognition of squamous cell carcinoma YD-38 cells using a convolutional neural network (CNN). First, a CNN classification model for the characteristics of YD-38 cell images is constructed. Then, pretraining and dropout technology are used to improve and optimize the proposed CNN model to improve the robustness of the model. In this paper, the miR mimic group and the miR blank group and the PI3K/AKT pathway inhibitor Wortmannin were selected to jointly treat YD-38 cells. The expression of mRNA in miR-1301 in HGF-1 was determined using RT-PCR (real and real-time fluorescence and YD-38 cells). The blank plasmids and the miR-1301 mimic (miR-1301 mimic) were transfected into YD-38 cells. The experiments were divided into two groups in the miR-1301 blank group and the miR-1301 simulation groups, respectively. The proliferation capacity of YD-38 cells was prepared in 1.5 ml sterile EP tubes and then diluted with medium for the proliferation of the cells. The scratch test and Transwell test were used to detect the effect of miR-1-3p on the migration and invasion of liver cancer cells. In this paper, CCK-8 experiment, clone formation experiment, flow cytometry, scratch experiment, and Transwell chamber experiment are used to analyze the effects of target gene CAAP1 on the proliferation, apoptosis, migration, and invasion of liver cancer cells. This paper uses CCK-8 to detect five kinds of the effect of miRNA on the proliferation ability of liver cancer cells and the effect of miR-1-3p on the proliferation ability of liver cancer cells. Experimental studies have shown that, compared with the miR blank group, the expression of PI3K and p-AKT was significantly downregulated in the miR mimic group after 24, 48, and 72 hours and the phosphorylation level of AKT was also significantly reduced (P < 0.05).

LncRNA RSU1P2-microRNA let-7a-Testis-Expressed Protein 10 axis modulates tumorigenesis and cancer stem cell-like properties in liver cancer

ABSTRACT LncRNAs exert important functions in the modulation of tumorigenesis and cancer stem cell-like properties in liver cancer. However, the role of LncRNA Ras suppressor protein 1 pseudogene 2 (RSU1P2) in modulating tumorigenesis and cancer stem cell-like properties in liver cancer is still not known. In this study, the expression of LncRNA RSU1P2 was significantly elevated in liver cancer tissues and cells. Besides, knockdown of RSU1P2 repressed cell viability, invasion, epithelial-mesenchymal transition (EMT) of liver cancer cells and the expressions of cancer stem cell-related genes, whereas facilitated the apoptosis of liver cancer cells. In addition, LncRNA RSU1P2 can interact with microRNA let-7a (let-7a), and repress let-7a expression. Testis-Expressed Protein 10 (Tex10) was identified to be a target of let-7a, and let-7a repressed Tex10 expression. Finally, RSU1P2 knockdown suppressed tumor volume, tumor weight, and EMT in a xenograft model. Therefore, LncRNA RSU1P2 promotes tumorigenesis and cancer stem cell-like properties in liver cancer through let-7a/Tex10 pathway.

Promotion of HepG2 cell apoptosis by Sedum emarginatum Migo and the mechanism of action

BackgroundSedum emarginatum Migo(S. emarginatum) has anti-tumor and anti-oxidant effects. This study aimed to screen the extractions of S. emarginatum against liver cancer in vitro and explore its anti-liver cancer mechanism.MethodsThe CCK-8(Cell Counting Kit-8) method was used to detect the inhibitory effect of different extracts of S. emarginatum on the proliferation of liver cancer HepG2 cells. The morphological changes of the cells after administration were observed with microscopy, cell apoptosis was detected by flow cytometry, and the expression of Bax, Bcl-2 and Caspase-3 mRNA in the cells were detected by RT-PCR (Reverse Transcription-Polymerase Chain Reaction) to explore the mechanism of action.ResultsCCK-8 method test results showed that among the different extracts of S. emarginatum, the ethyl acetate extract(1000 μg/ml, 2000 μg/ml, 2500 μg/ml, 3000 μg/ml) and n-butanol extract(1000 μg/ml, 2000 μg/ml, 2500 μg/ml, 3000 μg/ml) have the strongest inhibitory effect on the proliferation of HepG2 cells. In these 4 concentrations, the inhibitory effect increased as the concentration increased. The IC50 of the ethyl acetate extract on HepG2 cells was less than that of the n-butanol extract, so the ethyl acetate extract has a better proliferation inhibitory effect on HepG2 cells than the n-butanol extract, followed by the 70% ethanol extract(3000 μg/ml) and the water extract(3000 μg/ml), petroleum ether extract was the weakest. The results of microscopy showed that ethyl acetate extract caused hepatocarcinoma HepG2 cell morphology changed, cell density decreased, and suspension cells increased. Moreover, the results of flow cytometry showed that the ethyl acetate extract of S. emarginatum could induce HepG2 cell apoptosis at the concentrations of 2500μg/ml and 3000μg/ml. RT-PCR results showed that the expression of Bax mRNA was up-regulate by the middle(2500 μg/ml) and high(3000 μg/ml) dose groups of ethyl acetate extract. The expression of Caspase-3 mRNA was up-regulated by the low(2000 μg/ml), medium(2500 μg/ml) and high(3000 μg/ml) dose groups of ethyl acetate extract. The expression of Bcl-2 mRNA was down-regulated by the high(3000 μg/ml) dose group of ethyl acetate extract.ConclusionThe ethyl acetate extract of S. emarginatum has the best effect on human liver cancer HepG2 cells. Its anti-hepatocellular mechanism may be related to affect the expression of apoptosis genes (Bax, Bcl-2 and Caspase-3mRNA) and promote the apoptosis of liver cancer cells. It provided a reference for the research and development of drugs for the treatment of liver cancer.

Combination treatment with sorafenib and wh-4 additively suppresses the proliferation of liver cancer cells.

Sorafenib is currently used to treat hepatocellular carcinoma (HCC). However, the development of chemoresistance to sorafenib is a major limitation for sorafenib-based therapy in patients with HCC. In the present study, the effect of the combination therapy of sorafenib and wh-4 on the proliferation of liver cancer cells was investigated. The results showed that sorafenib with wh-4 additively suppressed the proliferation of liver cancer cells. The colony formation of liver cancer cells decreased significantly in response to the combination treatment of sorafenib with wh-4, and it also induced the apoptosis of liver cancer cells. Western blot analysis demonstrated decreased expression of Bcl2, and increased expression of Bax in liver cancer cells treated with a combination of sorafenib and wh-4. Moreover, the migration of liver cancer cells was inhibited. The combination treatment of sorafenib with wh-4 reduced the expression levels of ABCB1 and ABCG2 which are responsible for resistance. Finally, STAT3 overexpression abolished the proliferation inhibition effect of sorafenib with wh-4 on liver cancer cells, and sorafenib and wh-4 suppressed the proliferation of liver cancer cells by STAT3 pathway. Together, these results suggest that sorafenib-wh4 combination treatment is a potential novel therapeutic approach to suppress the proliferation of liver cancer cells.

Harmine reinforces the effects of regorafenib on suppressing cell proliferation and inducing apoptosis in liver cancer cells.

The overall outcomes for patients with advanced liver cancer are far from satisfactory, and the development of more effective therapeutic strategies for liver cancer is required. Sulforhodamine blue and colony formation assays were performed to detect the proliferation of liver certain cancer cells, including HepG2 and Hep3B. Western blotting was also preformed to detect the expression of indicated proteins, including cleaved-caspase-3, cleaved-poly (ADP-ribose) polymerase, dual-specificity tyrosine phosphorylation kinase 1A (DYRK1A), PARP-1/2, GAPDH, myeloid cell leukemia-1, phosphorylated-AKT (Ser473), caspase-3, α-tubulin and AKT. PI staining was used to detect cell death. In the present study, DYRK1A knockdown significantly enhanced the anti-liver cancer effect of regorafenib in vitro. Furthermore, DYRK1A inhibitor harmine together with regorafenib provided synergistic anti-liver cancer activity by suppressing cell proliferation. In addition, harmine significantly enhanced regorafenib-induced cell death in liver cancer cells. It has been reported that AKT signaling is activated in regorafenib-resistant cancer cells and plays a crucial role in the regulation of cellular sensitivity to regorafenib. In the present study, AKT was activated in regorafenib-treated cells, and harmine could suppress the activation of AKT and reinforce the anti-cancer effects of regorafenib via regulating AKT in liver cancer cells. These data indicated that harmine enhanced the anti-cancer effects of regorafenib on suppressing cell proliferation and inducing apoptosis in liver cancer cells via regulating the activation of AKT, and harmine plus regorafenib may be a potential therapeutic regimen for treating patients with liver cancer.

Effects of new bone marrow mesenchymal stem cell (BMSC)-liposome nanoparticles on DNA methylation status of hepatitis B-related liver cancer

Primary liver cancer is the most common tumor in China, with high morbidity and mortality. Nanotechnology has made continuous progress in recent years. In this study, new liposome nanoparticles were used to assemble the bone marrow mesenchymal stem cell (BMSC)-liposome nano-drug delivery system, to explore molecular mechanism of this technology in anti-HBV-related liver cancer. In this study, human hepatitis Brelated liver cancer cells were exposed to the novel BMSC-liposome nano-drug delivery system, and specific methylation analysis PCR (MSP) was used to detect cell apoptosis. Flow cytometry analysis was used to test cell cycle. Proliferation of human hepatitis B-related liver cancer cell line HepG2 was analyzed by MTT, while DNA methyltransferase (DNMT)/hepatitis B virus X protein (HBx) methylation status was detected by real time PCR. The new liposomal nanoparticle BMSC nano-drug delivery system increased the rate of cell apoptosis, inhibited the proliferation of HepG2, and blocked the cells in the G2/M phase. In addition, the new liposomal nanoparticle BMSC nano-drug delivery system reduced the content of hepatitis B virus X protein (HBx) in the HepG2 cells, and regulated virus replication by controlling the expression of methyltransferase (DNMT). DNA methylation level is one of the criteria for evaluating virus replication. The results from this study suggest that low-level methylation can contribute to the occurrence and development of tumors, and regional CpG island hypermethylation can increase DNase, to effectively promote the development of viral related diseases. HBx can effectively promote the progress of liver cancer through the expression of DNMT. In this study, a novel BMSC-liposome drug delivery system effectively controlled the replication of hepatitis B virus and increased the apoptosis of liver cancer cells. This process is closely related to inhibition of DNA methylase and promotion of HBx methylation.

Propofol suppresses proliferation, migration, invasion, and tumor growth of liver cancer cells via suppressing cancer susceptibility candidate 9/phosphatase and tensin homolog/AKT serine/threonine kinase/mechanistic target of rapamycin kinase axis.

Propofol is a commonly used drug for sedation and general anesthesia during cancer surgery. Previous studies indicate that propofol exerts anti-tumor effect in various cancers. The aim of this study was to investigate the underlying molecular mechanism of propofol in liver cancer. The effects of propofol on liver cancer cells were evaluated by cell viability assay, colony formation assay, and tumor xenograft model. Dysregulated lncRNAs of propofol-treated liver cancer cells were evaluated by transcriptome RNA sequencing. The underlying molecular mechanisms of lncRNA cancer susceptibility candidate 9 (CASC9) in propofol-induced anti-tumor effects were evaluated by western blot, quantitative real-time polymerase chain reaction (qRT-PCR), wound scratch healing assay, transwell cell migration and invasion assay, TUNEL staining, fluorescence in situ hybridization, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP). We found that propofol suppressed proliferation, migration, invasion, and tumor xenograft growth of liver cancer cells in a dose-dependent manner. Exosomes transfer from propofol-treated cells inhibited proliferation, migration, and invasion and promoted apoptosis of liver cancer cells. Transcriptional profiling of propofol-treated liver cancer cells identified CASC9 as significantly downregulated lncRNA in cells and exosomes. Enforced CASC9 expression partially rescued the inhibitory effects of propofol on liver cancer cells. Furthermore, CASC9 was found to interact directly with EZH2 and epigenetically regulated PTEN expression. Restoration of CASC9 partially abrogated the inhibition of propofol on Akt/mTOR signaling. Our results indicated that propofol exerted anti-tumor effects by downregulating CASC9, and subsequently suppressed Akt/mTOR signaling. Our findings provided a novel insight into propofol-induced anti-tumor effects in liver cancer.

MiR-15a-5p Regulates Liver Cancer Cell Migration, Apoptosis and Cell Cycle Progression by Targeting Transcription Factor E2F3.

Liver cancer is a prevalent tumor with high incidence and mortality. MicroRNAs participate in cancer pathogenesis and miR-15a-5p may influence tumor suppression in many cancers. Herein, we analyzed the effect of miR-15a-5p in liver cancer cell migration, apoptosis, and the cell cycle. RT-PCR was performed to measure miR-15a-5p expression levels, transwell assays were applied to investigate the effect of miR-15a-5p on cell migration, and flow cytometry was performed to explore the impact of miR-15a-5p on apoptosis and the cell cycle in Hep3B and HepG2 cells. Luciferase reporter assays and Western blotting were employed to determinate the relationship between E2F3 and miR-15a-5p in liver cancer cells. Expression of E2F3 was detected by bioinformatics analysis and RT-PCR in liver cancer. Small interfering RNA (si-RNA) was used to silence E2F3 expression and assess the effect on migration, apoptosis, and the cell cycle in Hep3B/HepG2 cells. The results demonstrated that miR-15a-5p was downregulated in human liver cancer tissue, and enhancing the expression of miR-15a-5p suppressed migration in liver cancer cells, induced apoptosis, and caused G1 phase arrest. In vivo assays were further performed and miR-15a-5p inhibited the growth of liver cancer. miR-15a-5p appeared to target E2F3, and RT-PCR and bioinformatic analyses indicated that E2F3 expression was higher in liver cancer than control tissues. Silencing E2F3 expression decreased cell migration, induced apoptosis, and caused G1 phase arrest in Hep3B/HepG2 cells. These findings indicate that miR-15a-5p regulates liver cancer cell migration, apoptosis, and growth by targeting E2F3. Thus, miR-15a-5p may act as a suppressor role in liver cancer.