Liver Cancer Cell Line HepG2 Research Articles

Rhamnetin decreases the expression of HMG-CoA reductase gene and increases LDL receptor in HepG2 cells

Context: Rhamnetin is a naturally occurring methylated derivative of quercetin. This flavonoid is abundant in Syzygium aromaticum, Coriandrum sativum Prunus cerasus, and Rhamnus spp. Aims: To evaluate the effects of rhamnetin on HMG-CoA reductase and low-density lipoprotein receptor (LDLR) gene and protein expressions in the HepG2 hepatoma cell line. Methods: The expression of HMG-CoA reductase and LDLR genes and proteins were studied in HepG2 liver cancer cell line by PCR, Western blot, and indirect ELISA, as well as their antioxidant activity. Results: Rhamnetin was non-toxic up to 200 μM on HepG2 at 24, 48, and 72 h. Rhamnetin (25 µM) upregulated LDLR gene expression by 1.66 folds compared to 3.12 folds exerted by the well-known hypocholesterolemic drug simvastatin. Rhamnetin (100 µM) increased the expression of LDLR protein at the cell membrane, while the other concentrations produced no significant change from the control (vehicle-treated). In HepG2 cell lysate, LDLR was increased by 50 µM of rhamnetin. Also, rhamnetin increased SOD activity significantly by 100.98, 86.28, and 100.98% by the concentrations 25, 50, and 100 µM, respectively. Using the same concentrations, rhamnetin reduced H2O2 levels by 50, 67, and 76.34%, respectively. Conclusions: This study demonstrated for the first time that rhamnetin reduced HMG-CoA reductase gene expression and increased LDLR in HepG2 cells.

Smart Drug Delivery Systems Based on Single-Wall Carbon Nanotubes Loaded with Nanocurcumin Extract for Cancer Therapy and Toxicity

The main objective of the study is to prepare smart drug delivery systems based on single-wall carbon nanotubes. In this study, nanocurcumin (N.Cur) was loaded onto SWCNTs containing polyethylene glycol (PEG) and polyethyleneimine (PEI), which includes amino groups — this led to the successful production of PEG-PEI-SWCNTs. XRD, UV-Vis, and TEM techniques were employed to investigate the spectral and structural properties of (PEG-PEI-SWCNTs-N.Cur). The PEG-PEI-SWCNTs showed distinct crystalline structures and flaws, as well as a larger interlayer spacing, as evidenced by XRD patterns. After loading N. Cur, TEM analysis confirmed the presence of curcumin extract. UV-Vis absorbance peaks at 289, 300.98, (282,425), and (273,431) nm appear to be linked to SWCNTs, PEG-PEI-SWCNTs, N. Curcumin extract, and PEG-PEI-SWCNTs-N, respectively. After exposure to a variety of produced SWNTs and PEG-PEI-SWCNTs at concentrations ranging from 6.25 to 100 g/ml for 72 hours, the rate of growth inhibition in cancer cells including the liver cancer HepG2 cell line—was assessed. The cancer cells were found to be very dangerous by the cytotoxicity testing.

Curcumin nanocapsules effect in apoptotic processes, gene expression, and cell cycle on Hep-G2 cell lines.

Curcumin has antioxidant and antiproliferative properties, and its therapeutic effect must be considered. Nanocurcumin capsules showed a potential increase against in vitro biological cancer. This study sought to determine how curcumin nanoparticles and nanocapsules affected the expression of p53, Bcl-2, Bax, and Bax in a liver cancer cell line (Hep-G2). Mechanisms of apoptosis were also examined in this cell line. This study used quantitative real-time polymerase chain reaction (qRT-PCR) to analyze the p53, Bcl-2, Bax, and Caspase-3 gene pathways and to evaluate the molecular mechanisms responsible for the efficacy of curcumin nanoparticles (CNPs) and curcumin nanocapsules (CNCs) against liver cell lines. Flow cytometry was used to check for signs of apoptosis and the cell cycle. Curcumin nanocapsules produced by the ball milling process at 90min significantly boosted the populations of apoptotic cells in a dose- and time-dependent manner. The mRNA expression analysis revealed that the proapoptotic Bax, Caspase-3, and the tumor suppressor gene p53 were upregulated throughout the process started by curcumin nanocapsules and decreased in the Bcl-2/Bax ratio. This research provides a fresh understanding of the molecular mechanisms behind the liver cancer-fighting abilities of curcumin nanoparticles. Curcumin nanocapsules produced through a unique mechanical technique can be used as an anticancer agent.

PH and Thermoresponsive PNIPAm-co-Polyacrylamide Hydrogel for Dual Stimuli-Responsive Controlled Drug Delivery.

The therapeutic delivery system with dual stimuli-responsiveness has attracted attention for drug delivery to target sites. In this study, we used free radical polymerization to develop a temperature and pH-responsive poly(N-isopropyl acrylamide)-co-poly(acrylamide) (PNIPAM-co-PAAm). PNIPAm-co-PAAm copolymer by reacting with N-isopropyl acrylamide (NIPAm) and acrylamide (Am) monomers. In addition, the synthesized melamine-glutaraldehyde (Mela-Glu) precursor was used as a cross-linker in the production of the melamine cross-linked PNIPAm-co-PAAm copolymer hydrogel (PNIPAm-co-PAAm-Mela HG) system. The temperature-responsive phase transition characteristics of the resulting PNIPAM-co-PAAm-Mela HG systems were determined. Furthermore, the pH-responsive drug release efficiency of curcumin was investigated under various pH and temperature circumstances. Under the combined pH and temperature stimuli (pH 5.0/45 °C), the PNIPAm-co-PAAm-Mela HG demonstrated substantial drug loading (74%), and nearly complete release of the loaded drug was accomplished in 8 h. Furthermore, the cytocompatibility of the PNIPAm-co-PAAm-Mela HG was evaluated on a human liver cancer cell line (HepG2), and the findings demonstrated that the prepared PNIPAm-co-PAAm-Mela HG is biocompatible. As a result, the PNIPAm-co-PAAm-Mela HG system might be used for both pH and temperature-stimuli-responsive drug delivery.

In vitro evaluation of immunomodulatory, anti-diabetic, and anti-cancer molecular mechanisms of Tribulus terrestris extracts

Dampened immunity and impaired wound healing in diabetic patients may lead to diabetic foot ulcer disease, which is the leading cause of limb amputations and hospitalization. On the other hand, cancer is the most significant cause of mortality globally, accounting for over 10 million fatalities in 2020, or nearly one in every six deaths. Plants and herbs have been used to treat chronic diseases due to their essential pharmaceutical attributes, such as mitigating drug resistance, ameliorating systemic toxicities, reducing the need for synthetic chemotherapeutic agents,and strengthening the immune system. The present study has been designed to evaluate the effects of Tribulus terrestris on wound healing, cytotoxic and anti-inflammatory responses against HepG-2 liver cancer cell line. Two solvents (methanol and ethanol) were used for root extraction of T. terrestris. The wound healing potential of the extracts was studied on diabetic cell culture line by scratch assay. The anti-oxidant and cytotoxic potentials were evaluated by in vitro assays against HepG2 cell line. The methanolic root extract resulted in the coverage of robust radical scavenging or maximum inhibition of 66.72%,potent cytotoxic activity or reduced cell viability of 40.98%, and anti-diabetic activity having mighty α-glucosidase inhibition of 50.16% at a concentration of 80 μg/ml. Significant reduction in the levels of LDH leakage (56.38%), substantial ROS (48.45%) and SOD (72.13%) activities were recorededMoreover, gene expression analysis demonstrated the down-regulation of inflammatory markers (TNF-α, MMP-9, Bcl-2, and AFP) in HepG-2 cells when treated with T.terresteris methanolic extract as compared to stress. Furthermore, the down-regulation of inflammatory markers was validated through ELISA-mediated protein estimation of IL-1β and TNF-α. It is expected that this study will lay a foundation and lead to the development of efficient but low-cost, natural herbs extract-based dressing/ointment for diabetic patients and identify potential drug metabolites to treat out-of-whack inflammatory responses involved in cancer onset, progression, and metastasis.

Research on flavonoids collection, activity assay and initial steps to create tea from Camellia tamdaoensis Hakoda et Ninh

The Camellia tamdaoensis Hakoda et Ninh contains many useful phenolic compounds for human health, among them, flavonoids showed many biological activities such as antibacterial, anti-inflammatory. In this study, we used the recovery extract method to collect concentrated solutions with high flavonoid content from golden tea leaves, in which ethanol served as solvents at the temperature of 70°C for 1 hour . The high golden tea leaves showed good antibacterial properties with Gram (+), Gram (-) and fungi, demonstrate toxicity to HEPG2 liver cancer cell line with IC50 100 ± 2.77 µg/ml. The process of creating tea bags from golden tea leaves with flavonoid supplements was completed. The ground golden tea leaves were sprayed with a solution containing flavonoids from 0.33 - 0.67 mg extract per extract grams of golden leaves, then dry until reaching a constant mass at 50°C. The product finally was packed into filter bags and investigated in terms of the quality of taste and color according to TCVN 3218: 2012. The flavonoid content in this product was 1.6 times higher than that of natural materials. This research’s results show the potential to develop golden tea products containing high flavonoids in the future.

Optimized pressurized hot water extraction, HPLC/LC-MS characterization, and bioactivity of Tetrapleura tetraptera L. dry fruit polyphenols.

Despite the global preference for green extraction methods in the recovery of plant bioactives, Tetrapleura tetraptera fruit polyphenols (TTP) are yet to receive considerable attention. For the first time, pressurized hot water extraction (PHWE) of TTP was optimized for total phenol content (TPC) and antioxidant activity (AA) using the Box Behnken design of response surface methodology. Predictor variables were time, temperature, and liquid-to-solid ratio. An optimum solution with a desirability of 0.805 was selected and parameters were 43min, 220°C, and 60ml g-1 liquid-to-solid ratio, yielding TPC of 8.92mg gallic acid equivalent per gram of sample on dry weight basis (GAE g-1 dw-1 ) and AA of 70.35%. Purified, optimized TTP were characterized and quantified using HPLC/LC-MS. PHWE mainly extracted rutin (379.04µg g-1 ), cyanidin-3-O-glucoside (chloride) (299.55µg g-1 ), naringenin 7-O-glucoside (240.11µg g-1 ), p-coumaric acid (177.28µg g-1 ), isorientin (150.43µg g-1 ), and gallic acid (118.06µg g-1 ) whereas cyanidin-3-O-glucoside (chloride) (83.27µg g-1 ), protocatechuic acid (61.37µg g-1 ), rutin (28.03µg g-1 ), and gallic acid (22.62µg g-1 ) were mainly extracted by hot water extraction, which was a control. PHWE-obtained TTP showed higher cellular antioxidant activity, cytotoxicity in human liver cancer cell lines (HepG2), and antimicrobial property against Escherichia coli, Staphylococcus aureus, and Bacillus subtilis than control. The potential mechanisms underlying the biological activities of some of the major polyphenols extracted were briefly discussed. Considering the wide use of the T. tetraptera (TT) fruit in Africa in foods and medicine, the use of more efficient green extraction methods such as PHWE is recommended. PRACTICAL APPLICATION: This study serves as a baseline for optimizing pressurized hot water extraction, purification, identification, and quantification of Tetrapleura tetraptera polyphenols (TTP) and their biological activities, being the first of its kind. The varied biological effects shown can be exploited further for applications of TTP as nutraceutical agents and preservatives in foods in different forms. Also, the high amounts of gallic acid and other phenolic acids and flavonoids confirmed in this study make TTP good candidates for the development of metal-phenol network nanoparticles to enhance adequate solubility and distribution in food systems in light of the above proposed applications.

Role of AHR, NF-kB and CYP1A1 crosstalk with the X protein of Hepatitis B virus in hepatocellular carcinoma cells

In this study, it was aimed to elucidate the interaction between aryl hydrocarbon receptor (AHR), nuclear factor-kappa B (NF-kB), and cytochrome P4501A1 (CYP1A1) with hepatitis B virus X protein (HBX) in a human liver cancer cell line (HepG2) transfected with HBX. First, AHR, NF-kB, and CYP1A1 genes were cloned into the appropriate region of the CheckMate mammalian two-hybrid recipient plasmids using a flexi vector system. Renilla and firefly luciferases were quantified using the dual-luciferase reporter assay system to measure the interactions. Secondly, transient transfections of CYP1A1 and NF-kB (RelA) were performed into HBX–positive and HBX–negative HepG2 cells. The mRNA expression of CYP1A1 and NF-kB genes were confirmed with RT-PCR, and cell viability was measured by WST-1. Further verification was assessed by measuring the activity and protein level of CYP1A1. Additionally, CYP1A1/HBX protein–protein interactions were performed with co-immunoprecipitation, which demonstrated no interaction. These results have clearly shown that the NF-kB and AHR genes interact with HBX without involving CYP1A1 and HBX protein–protein interactions. The present study confirms that AHR and NF-kB interaction plays a role in the HBV mechanism mediated via HBX and coordinating the carcinogenic or inflammatory responses; still, the CYP1A1 gene has no effect on this interaction.

Curcumin based pyrazole-thiazole hybrids as antiproliferative agents: Synthesis, pharmacokinetic, photophysical properties, and docking studies

A series of new curcumin pyrazole-thiazole hybrids (C1-C8) were synthesized and characterized by fundamental spectral analysis. The synthesized compounds were tested for antiproliferative activity against the colorectal cancer cell line (COLO-205), breast cancer cell line (MCF-7), liver cancer cell line (HepG-2), lung cancer cell line (A549), and cervical cancer cell line (HeLa) using cisplatin as a positive control. The compounds C7 (IC50 values of 8.57 ± 1.09 µM for COLO-205, 9.22 ± 0.73 µM for MCF-7, 16.95 ± 1.16 µM for HepG-2, 8.48 ± 1.36 µM for A549, and 7.22 ± 1.08 µM for HeLa), C2, and C5 displayed the most potent antiproliferative activity against the growth of all tested cell lines. For the three compounds (C2, C5, and C7), which were shown to have high in vitro anti-cancer activity, we have carried out a kinase inhibitory assay against the EGFR and HER2, where the compound C7 has exhibited double inhibitory potency towards the EGFR when compared to reference erlotinib. Furthermore, in silico molecular docking studies on EGFR (PDB ID: 4HJ0) and HER2 (PDB ID: 3P0Z) proteins revealed that the potent ligands exhibited higher affinity with an active pocket of receptors showing strong hydrogen bond interactions. The compounds C5 and C2 showed potent antioxidant activity. In addition, the drug-likeness of the hybrids was assessed by predicting their physicochemical, pharmacokinetic (ADME), toxicity profiles, and photophysical properties.

Synthesis and appraisal of dalbergin-loaded PLGA nanoparticles modified with galactose against hepatocellular carcinoma: In-vitro, pharmacokinetic, and in-silico studies.

Hepatocellular carcinoma (HCC) is a common malignancy which affects a substantial number of individuals all over the globe. It is the third primary cause of death among persons with neoplasm and has the fifth largest mortality rate among men and the seventh highest mortality rate among women. Dalbergin (DL) is described to be effective in breast cancer via changing mRNA levels of apoptosis-related proteins. DL belongs to neoflavonoids, a drug category with low solubility and poor bioavailability. We created a synthetic version of this naturally occurring chemical, DL, and then analyzed it using 1H-NMR, 13C-NMR, and LC-MS. We also made PLGA nanoparticles and then coated them with galactose. The design of experiment software was used to optimize DL-loaded galactose-modified PLGA nanoparticles. The optimized DL-nanoformulations (DLF) and DL-modified nanoformulations (DLMF) were analyzed for particle size, polydispersity index, shape, and potential interactions. In-vitro experiments on liver cancer cell lines (HepG2) are used to validate the anti-proliferative efficacy of the modified DLMF. The in-vitro research on HepG2 cell lines also demonstrated cellular accumulation of DLF and DLMF by FITC level. The in-vitro result suggested that DLMF has high therapeutic effectiveness against HCC. In-vivo pharmacokinetics and bio-distribution experiments revealed that DLMF excelled pristine DL in terms of pharmacokinetic performance and targeted delivery, which is related to galactose's targeting activity on the asialoglycoprotein receptor (ASGPR) in hepatic cells. Additionally, we performed an in-silico study of DL on caspase 3 and 9 proteins, and the results were found to be -6.7kcal/mol and -6.6kcal/mol, respectively. Our in-silico analysis revealed that the DL had strong apoptotic properties against HCC.

Studying the genotoxicity caused by sodium benzoate in liver cancer cell line (HEPG2) by comet assay

Objective: Genetic toxicity examines the health of those exposed to mutagenic agents and the mutagenic impacts of radiation and chemicals. The process of causing genetic alterations and DNA damage is known as mutagenesis. Therefore, it is vital to carry out research in this area at many levels and come up with suitable ways to stop or lessen the development of genetic toxicity. The sodium version of benzoic acid, sodium benzoate, is a common ingredient in both food and cosmetics. This study aims to explore the genotoxicity produced by sodium benzoate in the liver cancer cell line (HepG2) using the Comet assay because of the substance's widespread use. Method: The comet assay or single cell gel electrophoresis (SCGE) is a quick and accurate method for identifying and assessing DNA damage in single cells. One-way ANOVA and Tukey's multiple comparison posthoc test were used to examine the results, which were shown as the SD Mean of the report and the data connected to the Comet indices. The difference's significance threshold was set at p<0.0001. Findings: DNA damage was generated in the liver cancer cell line in the current investigation by sodium benzoate's genotoxicity at concentrations of 50, 100, and 150 micromolar (HepG2).

A Computational QSAR, Molecular Docking and In Vitro Cytotoxicity Study of Novel Thiouracil-Based Drugs with Anticancer Activity against Human-DNA Topoisomerase II.

Computational chemistry, molecular docking, and drug design approaches, combined with the biochemical evaluation of the antitumor activity of selected derivatives of the thiouracil-based dihydroindeno pyrido pyrimidines against topoisomerase I and II. The IC50 of other cell lines including the normal human lung cell line W138, lung cancer cell line, A549, breast cancer cell line, MCF-7, cervical cancer, HeLa, and liver cancer cell line HepG2 was evaluated using biochemical methods. The global reactivity descriptors and physicochemical parameters were computed, showing good agreement with the Lipinski and Veber’s rules of the drug criteria. The molecular docking study of the ligands with the topoisomerase protein provides the binding sites, binding energies, and deactivation constant for the inhibition pocket. Various biochemical methods were used to evaluate the IC50 of the cell lines. The QSAR model was developed for colorectal cell line HCT as a case study. Four QSAR statistical models were predicted between the IC50 of the colorectal cell line HCT to correlate the anticancer activity and the computed physicochemical and quantum chemical global reactivity descriptors. The predictive power of the models indicates a good correlation between the observed and the predicted activity.

Thermo-Sensitive Poly (N-isopropylacrylamide-co-polyacrylamide) Hydrogel for pH-Responsive Therapeutic Delivery.

Stimuli-response polymeric nanoparticles have emerged as a carrier system for various types of therapeutic delivery. In this study, we prepared a dual pH- and thermo-sensitive copolymer hydrogel (HG) system (PNIPAm-co-PAAm HG), using N-isopropyl acrylamide (NIPAm) and acrylamide (AAm) as comonomers. The synthesized PNIPAm-co-PAAm HG was characterized using various instrumental characterizations. Moreover, the PNIPAm-co-PAAm HG’s thermoresponsive phase transition behavior was investigated, and the results showed that the prepared HG responds to temperature changes. In vitro drug loading and release behavior of PNIPAm-co-PAAm HG was investigated using Curcumin (Cur) as the model cargo under different pH and temperature conditions. The PNIPAm-co-PAAm HG showed pH and temperature-responsive drug release behavior and demonstrated about 65% Cur loading efficiency. A nearly complete release of the loaded Cur occurred from the PNIPAm-co-PAAm HG over 4 h at pH 5.5 and 40 °C. The cytotoxicity study was performed on a liver cancer cell line (HepG2 cells), which revealed that the prepared PNIPAm-co-PAAm HG showed good biocompatibility, suggesting that it could be applied as a drug delivery carrier. Moreover, the in vitro cytocompatibility test (MTT assay) results revealed that the PNIPAm-co-PAAm HG is biocompatible. Therefore, the PNIPAm-co-PAAm HG has the potential to be useful in the delivery of drugs in solid tumor-targeted therapy.

Synthesis, Characterization, and Cytotoxicity of New Spirooxindoles Engrafted Furan Structural Motif as a Potential Anticancer Agent.

A new series of spirooxindoles based on ethylene derivatives having furan aryl moiety are reported. The new hybrids were achieved via [3 + 2] cycloaddition reaction as an economic one-step efficient approach. The final constructed spirooxindoles have four contiguous asymmetric carbon centers. The structure of 3a is exclusively confirmed using X-ray single crystal diffraction. The supramolecular structure of 3a is controlled by O···H, H···H, and C···C intermolecular contacts. It includes layered molecules interconnected weak C–H···O (2.675 Å), H···H (2.269 Å), and relatively short Cl···Br interhalogen interactions [3.4500(11)Å]. Using Hirshfeld analysis, the percentages of these intermolecular contacts are 10.6, 25.7, 6.4, and 6.2%, respectively. The spirooxindoles along with ethylene derivatives having furan aryl moiety were assessed against breast (MCF7) and liver (HepG2) cancer cell lines. The results indicated that the new chalcone 3b showed excellent activity in both cell lines (MCF7 and HepG2) with IC50 = 4.1 ± 0.10 μM/mL (MCF7) and 3.5 ± 0.07 μM/mL (HepG2) compared to staurosporine with 4.3 and 2.92 folds. Spirooxindoles 6d (IC50 = 4.3 ± 0.18 μM/mL), 6f (IC50 = 10.3 ± 0.40 μM/mL), 6i (IC50 = 10.7 ± 0.38 μM/mL), and 6j (IC50 = 4.7 ± 0.18 μM/mL) exhibited potential activity against breast adenocarcinoma, while compounds 6d (IC50 = 6.9 ± 0.23 μM/mL) and 6f (IC50 = 3.5 ± 0.11 μM/mL) were the most active hybrids against human liver cancer cell line (HepG2) compared to staurosporine [IC50 = 17.8 ± 0.50 μM/mL (MCF7) and 10.3 ± 0.23 μM/mL (HepG2)]. Molecular docking study exhibited the virtual mechanism of binding of compound 3b as a dual inhibitor of EGFR/CDK-2 proteins, and this may highlight the molecular targets for its cytotoxic activity.

A universal co-expression gene network and prognostic model for hepatic-biliary-pancreatic cancers identified by integrative analyses.

Hepatic, biliary and pancreatic cancers are a diverse set of malignancies with poor prognoses. It is possible that common molecular mechanisms are involved in the carcinogenesis of these cancers. Here, we identified LINC01537 and seven protein-coding genes by integrative analysis of transcriptomes of mRNAs, microRNAs and long non-coding RNAs from cholangiocarcinoma, hepatocellular carcinoma and pancreatic adenocarcinoma cohorts in TCGA. A predictive model constructed from seven biomarkers was established to successfully predict the survival rate of patients, which was then further verified in external cohorts. Additionally, patients with high-risk scores in our model were prone to epithelial-mesenchymal transition. Finally, activation of the biomarker PDE2A significantly attenuated migration and epithelial-mesenchymal transition in the HepG2 liver cancer cell line.

Antimicrobial and Anticancer Activity of Corydalis solida

Aim: The present study, it was aimed to evaluate the bioactive properties of Corydalis solida.
 Material and Methods: In the study, the anticancer activity of ethanolic extracts prepared from C. solida was determined on HCT116 colon cancer, AGS gastric cancer and HepG2 hepatocellular carcinoma cell lines and HUVEC cells, healthy control cell line. Well diffusion method was used to determine the antimicrobial properties of solida. For this purpose, ethanolic extracts were used for antimicrobial activity against four bacterial isolates (Escherichia coli, Bacillus cereus, Staphylococcus aureus and Klebsiella oxytoca) and three yeast strains (Candida albicans, C. tropicalis and C .glabrata).
 Results: Corydalis solida plant extract produced significant antiproliferative effect in HCT116 (colon cancer), AGS (gastric cancer) and HepG2 (liver cancer) cell lines. This effect was more remarkable in the HepG2 cell line. In addition, negligible cell death in HUVEC cells indicated that the plant was not toxic to healthy cells. Plant extract application also caused significant Caspase-3, 8 and 9 activation in HepG2 and HCT116 cells, consistent with the antiproliferative effect. Antimicrobial studies have shown that the extract made inhibition zone on bacteria.
 Conclusion: In the study, it was determined that the ethanol extract of Corydalis solida had anticancer effect. In addition, the extract had inhibitory properties on bacteria. The data obtained from the study are qualified to support further pharmacological studies.

The Effect of lncRNA-PVT1 on Liver Cancer Rats by Regulating the Expression of MMP9.

As a malignant tumor, liver cancer has a high lethality rate. The research on the pathogenesis of liver cancer is the key to the treatment of liver cancer. The latest research claims that lncRNA-PVT1 as a tumor gene participates in the generation and development of tumors by regulating matrix metalloproteinase MMP9. The purpose of this article is to explore the specific effect and mechanism of lncRNA-PVT1 on liver cancer rats by regulating the expression of MMP9. In this article, 50 rats are used as experimental subjects, the rats are divided into control group and observation group, and the liver cancer cell line HepG2 is cultured. The transplanted tumor liver cancer model was constructed by transfection of hair, the expression of lncRNA-PVT1 in the observation group was reduced by knockdown method, the expression levels and changes of lncRNA-PVT1 and MMP9 in the two groups were detected by PCR fluorescence method, and the difference between lncRNA-PVT1 and MMP9 was analyzed. The MTT method was used to detect the proliferation, migration, and invasion capabilities of the two groups of liver cancer cells (LCC) and to explore the effect of lncRNA-PVT1 on rat LCC by regulating the expression of MMP9. The results of the study showed that after knocking down the expression of lncRNA-PVT1 in the observation group, the expression of MMP9 also decreased. At the same time, the migration rate of LCC HepG2 decreased by 27.4%, the level of invasion ability decreased by 21.6%, and the proliferation rate of LCC decreased by 17.8%. Therefore, it can be seen that lncRNA-PVT1 plays a positive regulatory role on the expression of MMP9, and the expression of MMP9 promotes the proliferation, migration, and invasion of rat LCC.

Multi-spectroscopic characteristics of olive oil-based Quercetin nanoemulsion (QuNE) interactions with calf thymus DNA and its anticancer activity

Several types of biological functions have been reported for Quercetin, such as antioxidant and anticancer activities. The current study aimed to improve the solubility and stability of Quercetin’s nanoemulsions (QuNEs) produced under polar physiologic conditions and to clarify Quercetin’s interaction properties with calf thymus DNA (ctDNA) in its released form. The cytotoxicity of QuNE was analyzed by measuring the MTT assay in MCF-7 cells and caspase-9 gene expression in the HePG2 liver cancer cell line. Also, the ABTS antioxidant assay was performed for evaluating QuNE’s antioxidant activity. QuNE’s interaction with ctDNA was evaluated via running RLS and CD spectroscopy, viscometry, thermal denaturation, thermodynamic parameters (Van’t Hoff and Stern-Volmer diagrams), and molecular docking methods. The QuNE-released Quercetin significantly reduced viability of MCF-7 cells and induced caspase-9 up-regulation in HepG2 cancer cells. Further, compared with unreleased Quercetin, QuNE particles made complexes with ctDNA through hydrophobic interactions. The ΔH0, ΔS0, and binding constant (BC) indices for QuNE-ctDNA were measured at 68.36 KJ.mol−1, 308.42 J.mol-1K−1, and 0.04 × 104 and 2.49 × 104 M−1, respectively. Further, high antioxidant activity was measured for QuNE. QuNE was detected as the DNA groove binder agent. Considering QuNE’s ability in releasing Quercetin near ctDNA, it can be potentially used as an appropriate delivery transporting system which can successfully interact with DNA molecules in a groove binding manner to induce apoptotic effects.

DLK1-directed chimeric antigen receptor T-cell therapy for hepatocellular carcinoma.

Delta-like homologue 1 (DLK1), a transmembrane protein, is highly expressed in hepatocellular carcinoma (HCC). We explored whether DLK1-directed chimeric antigen receptor (CAR) T cells can specifically eliminate DLK1-positive HCC cells and serve as a therapeutic strategy for HCC immunotherapy. We first characterized a homemade anti-human DLK1 monoclonal antibody, sequenced the single-chain Fragment variable (scFv) and integrated it into the second-generation CAR lentiviral vector, and then developed the DLK1-directed CAR-T cells. The cytotoxic activities of DLK1-directed CAR-T cells against different HCC cells were evaluated in vitro and in vivo. The genetically modified human T cells with the DLK1-directed CARs produced cytotoxic activity against DLK1-positive HCC cells. Additionally, the DLK1-directed CARs enhanced T cell proliferation and activation in a DLK1-dependent manner. Interestingly, the DLK1-targeted CAR-T cells significantly inhibited both subcutaneous and peritoneal xenograft tumours derived from human liver cancer cell lines HepG2 or Huh-7. DLK1-directed CAR-T cells specifically suppresses DLK1-positive HCC cells in vitro and in vivo. This study provides a novel transmembrane antigen DLK1 as a potential therapeutic target appropriate for CAR-T cell therapy, which may be further developed as a clinical therapeutic strategy for HCC immunotherapy.

Therapeutic Effects of Crocin Alone or in Combination with Sorafenib against Hepatocellular Carcinoma: In Vivo & In Vitro Insights.

This study investigated the therapeutic effects of the phytochemical crocin alone or in combination with sorafenib both in rats chemically induced with hepatocellular carcinoma (HCC) and in human liver cancer cell line (HepG2). Male rats were randomly divided into five groups, namely, control group, HCC induced group, and groups treated with sorafenib, crocin or both crocin and sorafenib. HCC was induced in rats with a single intraperitoneal injection of diethylnitrosamine (DEN), then 2-acetylaminofluorene (2-AAF). The HCC-induced rats showed a significant decrease in body weight compared to animals treated with either or both examined drugs. Serum inflammatory markers (C-reactive protein (CRP); interleukin-6 (IL-6); lactate dehydrogenase (LDH), and oxidative stress markers were significantly increased in the HCC group and were restored upon treatment with either or both of therapeutic molecules. Morphologically, the HCC-induced rats manifested most histopathological features of liver cancer. Treatment with either or both of crocin and sorafenib successfully restored normal liver architecture. The expression of key genes involved in carcinogenesis (TNFα, p53, VEGF and NF-κB) was highly augmented upon HCC induction and was attenuated post-treatment with either or both examined drugs. Treatment with both crocin and sorafenib improved the histopathological and inflammation parameters as compared to single treatments. The in vivo anti-cancer effects of crocin and/or sorafenib were supported by their respective cytotoxicity on HepG2 cells. Crocin and sorafenib displayed an anti-tumor synergetic effect on HepG2 cells. The present findings demonstrated that a treatment regimen with crocin and sorafenib reduced liver toxicity, impeded HCC development, and improved the liver functions.