Hepatic Carcinoma Cells Research Articles

Evaluation of a Novel Phosphorylated Red Dragon Fruit Peel Pectin for Enhancement of Thermal Stability and Functional Activity.

Red dragon fruit peel, as a fruit waste, is rich in plant-based nutritional pectins that can be applied as food additives. The present study aims to characterize a novel phosphorylated red dragon fruit peel pectin (PRDFP-P) and to explore its functional activities. The thermal analysis, morphology analysis, antibacterial, antioxidant and antitumor activities of PRDFP-P were evaluated. The results showed that the phosphorylated derivative PRDFP-P had typical phosphate groups. Compared with the native red dragon fruit peel pectin (PRDFP), PRDFP-P possessed superior thermal stability and exhibited significant inhibition effects on Escherichia coli and Staphylococcus aureus. Moreover, the phosphate groups on the derivative PRDFP-P chains remarkably enhanced the scavenging ability of hydroxyl radicals and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. In addition, PRDFP-P showed a significant inhibition effect on growth of human hepatic carcinoma cells (HepG2) and the IC50 value was determined to be 248.69μg/mL (P< 0.05). Our results suggested that the phosphorylated derivative PRDFP-P might be potentially applied as stabilizing, thickening and gelling agents with functional activities in the food industry.

The Research Progress of Antiangiogenic Therapy, Immune Therapy and Tumor Microenvironment.

Anti-angiogenesis therapy, a promising strategy against cancer progression, is limited by drug-resistance, which could be attributed to changes within the tumor microenvironment. Studies have increasingly shown that combining anti-angiogenesis drugs with immunotherapy synergistically inhibits tumor growth and progression. Combination of anti-angiogenesis therapy and immunotherapy are well-established therapeutic options among solid tumors, such as non-small cell lung cancer, hepatic cell carcinoma, and renal cell carcinoma. However, this combination has achieved an unsatisfactory effect among some tumors, such as breast cancer, glioblastoma, and pancreatic ductal adenocarcinoma. Therefore, resistance to anti-angiogenesis agents, as well as a lack of biomarkers, remains a challenge. In this review, the current anti-angiogenesis therapies and corresponding drug-resistance, the relationship between tumor microenvironment and immunotherapy, and the latest progress on the combination of both therapeutic modalities are discussed. The aim of this review is to discuss whether the combination of anti-angiogenesis therapy and immunotherapy can exert synergistic antitumor effects, which can provide a basis to exploring new targets and developing more advanced strategies.

Green formulation of Ag nanoparticles by Hibiscus rosa-sinensis: Introducing a navel chemotherapeutic drug for the treatment of liver cancer

An eco-friendly biosynthesized Ag NPs immobilized Hibiscus rosa-sinensis extract has been introduced. The as-prepared nanoparticles were characterized using UV–Vis, SEM, and FT-IR analysis. In the FT-IR test, the presence of many antioxidant compounds with related bonds caused the excellent condition for reducing of silver in the silver nanoparticles. In UV–Vis, the clear peak in the wavelength of 428 nm indicated the formation of silver nanoparticles. The synthesized nanoparticles had very low cell viability and high anti-liver cancer activities dose-dependently against pleomorphic hepatocellular carcinoma (SNU-387), hepatic ductal carcinoma (LMH/2A), morris hepatoma (McA-RH7777), and novikoff hepatoma (N1-S1 Fudr) cell lines without any cytotoxicity on the normal cell line (HUVEC). The synthesized nanoparticles inhibited half of the DPPH molecules in the concentration of 78 µg/mL. Perhaps notable anti-liver cancer activities of the synthesized nanoparticles against common liver cancer cell lines are linked to their antioxidant activities.

Targeting of non-coding RNAs encoded by novel MYC enhancers inhibits the proliferation of human hepatic carcinoma cells in vitro

The proto-oncogene MYC is important for development and cell growth, however, its abnormal regulation causes cancer. Recent studies identified distinct enhancers of MYC in various cancers, but any MYC enhancer(s) in hepatocellular carcinoma (HCC) remain(s) elusive. By analyzing H3K27ac enrichment and enhancer RNA (eRNA) expression in cultured HCC cells, we identified six putative MYC enhancer regions. Amongst these, two highly active enhancers, located ~ 800 kb downstream of the MYC gene, were identified by qRT-PCR and reporter assays. We functionally confirmed these enhancers by demonstrating a significantly reduced MYC expression and cell proliferation upon CRISPR/Cas9-based deletion and/or antisense oligonucleotide (ASO)-mediated inhibition. In conclusion, we identified potential MYC enhancers of HCC and propose that the associated eRNAs may be suitable targets for HCC treatment.

Novel quinoline derivatives as antitumor agents against HepG2 cells: Synthesis, characterization, in silico, in vitro and docking studies

New quinoline derivatives based on the allyl and amino acid were prepared and characterized using elemental analysis, 1HNMR, 13CNMR spectra. Docking studies of synthesized compounds were performed in order to explore their binding with HepG2 (code: 5EQG protein) as human liver carcinoma. Some synthesized compounds were evaluated for them in vitro cytotoxic activity against the hepatic carcinoma cell line (HepG2). Among the tested compounds, compound 15d exhibited the most promising profile, being able to inhibit HepG2 (IC50 = 6.529 µg/ml).

MiR-145 Regulates the Chemoresistance of Hepatic Carcinoma Cells Against 5-Fluorouracil by Targeting Toll-Like Receptor 4 [Expression of Concern

MiR-145 Regulates the Chemoresistance of Hepatic Carcinoma Cells Against 5-Fluorouracil by Targeting Toll-Like Receptor 4 [Expression of Concern

β-Galactosidase-activated theranostic for hepatic carcinoma therapy and imaging.

A β-galactosidase activatable fluorescent turn-on theranostic Gal-CGem exhibits gemcitabine release specifically in β-galactosidase overexpressing hepatic carcinoma cells. The cytotoxicity of Gal-CGem in cancer cells is achieved through the apoptotic cell death pathway. Overall, Gal-CGem is a new frontline prodrug in cancer therapy that has provided antineoplastic information through fluorescence imaging.

MiR-10b-5p Suppresses the Proliferation and Invasion of Primary Hepatic Carcinoma Cells by Downregulating EphA2.

Objective To analyze the function of miR-10b-5p in suppressing the invasion and proliferation of primary hepatic carcinoma cells by downregulating erythropoietin-producing hepatocellular receptor A2 (EphA2). Material and Methods. Eighty-six hepatic carcinoma (HCC) tissue specimens and 86 corresponding adjacent tissue specimens were collected, and the mRNA expression of miR-10b-5p and Ephrin type-A receptor 2 (EphA2) in the specimens was determined using a reverse transcription-polymerase chain reaction (RT-PCR) assay. Western blot was employed to quantify EphA2, B-cell chronic lymphocytic leukemia/lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and Caspase-3 in the cells, and CCK8, Transwell assay, and flow cytometry were applied to evaluate the proliferation, invasion, and apoptosis of cells, respectively. Moreover, the dual luciferase reporter assay was utilized for correlation analysis between miR-10b-5p and EphA2. Results miR-10b-5p was lowly expressed in HCC, while EphA2 was highly expressed. Cell experiments revealed that miR-10b-5p overexpression or EphA2 knockdown could reduce cell proliferation, accelerate apoptosis, strongly upregulate Bax and Caspase-3, and downregulate Bcl-2. In contrast, miR-10b-5p knockdown or EphA2 overexpression gave rise to reverse biological phenotypes. Furthermore, dual luciferase reporter assay verified that miR-10b-5p was a target of EphA2, and the rescue experiment implied that transfection of pCMV-EphA2 or Si-EphA2 could reverse EphA2 expression and cell biological functions caused by miR-10b-5p overexpression or knockdown. Conclusions miR-10b-5p reduced HCC cell proliferation but accelerate apoptosis by regulating EphA2, suggesting it has the potential to be a clinical target for HCC.

Iron nanoparticles green-formulated by Coriandrum sativum leaf aqueous ‎extract: Investigation of its anti-liver cancer effects

IntroductionRecently, scientists have ‎understood that metallic nanoparticles especially iron nanoparticles have ‎excellent anticancer properties‎. A green, productive, and environmentally method was developed for the valuable study and the effective preparation of the biosynthesis of iron nanoparticles using aqueous extracts from the leaf of Coriandrum sativum as a result of reducing and stabilizing factor. The simplicity of the reaction, heterogeneous system, and easy work up are the benefits of the present method.Material and methodsThe as-prepared nanoparticles (FeNPs) was characterized using UV-Vis, SEM, and FT-IR. It has ‎been shown that the iron nanoparticles have spherical shape and uniform size.ResultsThe synthesized nanoparticles had very low cell viability and high anti-liver cancer activities ‎dose-dependently against pleomorphic hepatocellular carcinoma (SNU-387), hepatic ductal ‎carcinoma (LMH/2A), morris hepatoma (McA-RH7777), and novikoff hepatoma (N1-S1 Fudr) ‎cell lines without any cytotoxicity on the normal cell line (HUVEC). The synthesized ‎nanoparticles inhibited half of the DPPH molecules in the concentration of 132 µg/mL. Perhaps ‎notable anti-liver cancer activities of the synthesized nanoparticles against common liver cancer ‎cell lines are linked to their antioxidant activities. ‎ConclusionsOur results point out that the FeNPs from Coriandrum sativum extract are apposite stabilizing ‎agents, which serve as an effective anticancer agent against liver cancer cell lines.‎

Type-III interferon stimulated gene TRIM31 mutation in an HBV patient blocks its ability in promoting HBx degradation

TRIM5γ, together with TRIM31, has been shown to promote HBx ubiquitination and degradation. This study aimed to explore whether a patient with HCC (hepatic cell carcinoma) having a small nucleotide inserted into the TRIM31 gene, which made a shorter transcript stop at 768 bp, would result in blocking the activity of TRIM31 in promoting HBx degradation. Besides, this study aimed to determine the binding region of the TRIM31–TRIM5γ–HBx complex. HBV (Hepatitis B virus) infection was reported to induce type-III IFN but not type-I or type-II IFNs, here TRIM31 was found to be a type III rather than a type I stimulated gene, which was indispensable in inhibiting the hepatitis B virus replication by the interferon families. Thus, this study further identified the critical role of TRIM31 in the host–hepatitis B virus interaction.

MicroRNA-375 inhibits the malignant behaviors of hepatic carcinoma cells by targeting NCAPG2.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide. Emerging evidence has revealed the vital functions of microRNAs (miRNAs) in cancer malignant progressions. miR-375 has been verified to serve as an antioncogene in tumorigenesis and a potential therapeutic target in various types of cancer. In this study, we aimed to determine the role of miR-375 in the regulation of chemoresistance and metastasis of HCC. Differentially expressed miR-375 and NCAPG2 were externally validated using expression data from The Cancer Genome Atlas (TCGA) database. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression levels of miR-375 in HCC tissues and cell lines. miR-375 mimics and NCAPG2-overexpression were transfected into HepG2 and Huh7 cells to establish miR-375 overexpression models. Cell Counting Kit-8, Transwell, and flow cytometry experiments were conducted to monitor cell proliferation, migration, and apoptosis. The targeting relationship between miR-375 and non-SMC condensin II complex subunit G 2 (NCAPG2) was determined by qRT-PCR, western blot, and luciferase reporter gene assay. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted using Gene Set Enrichment Analysis (GSEA). The pathway enrichment analysis was used to predict the potential pathways for further study. miR-375 was significantly downregulated in HCC tissues and cells compared to adjacent tissue and normal hepatocyte cell line respectively while NCAPG2 was upregulated. The targeting relationship was verified by luciferase reporting assay, and miR-375 could target the 3'UTR of NCAPG2 mRNA and effectively suppress NCAPG2 protein expression. Replenishing of miR-375 significantly repressed HCC cell proliferation and migration, and induced cell apoptosis. Overexpression of NCAPG2 recovered those biological abilities in miR-375 overexpressed cells. Collective data suggested that miR-375 served as a tumor suppressor via regulating NCAPG2. Replenishing of miR-375 or knockout of NCAPG2 could be therapeutically exploited for HCC.

The role of Interventional Radiology in primary and metastatic liver disease – a short review of primary methods and therapy approaches

Primary and metastatic liver tumors are an increasing global health burden. As of 2020 colorectal cancer (CRC), which often presents with hepatic metastasis in the course of the disease was a second leading cause of cancer-related mortality worldwide. This was followed by hepatic cell carcinoma (HCC). Besides systemic therapies and surgical methods, which are not always applicable, many locoregional approaches were developed and are being increasingly implemented in the field of interventional radiology (IR) – both as primary and bridging procedures.&#x0D; The purpose of this article is to outline and briefly discuss these primary approaches used in IR in liver neoplastic disease.

Application and Research of Convolution Neural Network in MRI Image Classification and Recognition

The traditional hepaticcell carcinoma (HCC) pathological grading depends on biopsy, which will cause damage to the patient's body and is not suitable for everyone's pathological grading diagnosis. The purpose of this paper is to study the pathological grading of liver tumors on MRI images by using deep learning algorithm, so as to further improve the accuracy of HCC pathological grading. An improved network model based on SE-DenseNet is proposed. The nonlinear mapping relationship between feature channels is modeled and recalibrated using attention mechanism, and rich deep-seated features are extracted, so as to improve the feature expression ability of the network. The method proposed in this paper is verified on the data set including 197 patients, including 130 training sets and 67 test sets. The experimental results are evaluated by receiver operating characteristic (ROC) and area under the ROC curve (AUC). The improved SE-Densenet network achieves good results, and AUC 0.802 is obtained on the test set. The experimental results show that the method proposed in this paper can well predict the pathological grade of HCC.

Counteracting Action of Curcumin on High Glucose-Induced Chemoresistance in Hepatic Carcinoma Cells.

Along with direct anticancer activity, curcumin hinders the onset of chemoresistance. Among many, high glucose condition is a key driving factor for chemoresistance. However, the ability of curcumin remains unexplored against high glucose-induced chemoresistance. Moreover, chemoresistance is major hindrance in effective clinical management of liver cancer. Using hepatic carcinoma HepG2 cells, the present investigation demonstrates that high glucose induces chemoresistance, which is averted by the simultaneous presence of curcumin. Curcumin obviated the hyperglycemia-induced modulations like elevated glucose consumption, lactate production, and extracellular acidification, and diminished nitric oxide and reactive oxygen species (ROS) production. Modulated molecular regulators are suggested to play a crucial role as curcumin pretreatment also prevented the onset of chemoresistance by high glucose. High glucose instigated suppression in the intracellular accumulation of anticancer drug doxorubicin and drug-induced chromatin compactness along with declined expression of drug efflux pump MDR-1 and transcription factors and signal transducers governing the survival, aggressiveness, and apoptotic cell death (p53, HIF-1α, mTOR, MYC, STAT3). Curcumin alleviated the suppression of drug retention and nuclear condensation along with hindering the high glucose-induced alterations in transcription factors and signal transducers. High glucose-driven resistance in cancer cells was associated with elevated expression of metabolic enzymes HKII, PFK1, GAPDH, PKM2, LDH-A, IDH3A, and FASN. Metabolite transporters and receptors (GLUT-1, MCT-1, MCT-4, and HCAR-1) were also found upregulated in high glucose exposed HepG2 cells. Curcumin inhibited the elevated expression of these enzymes, transporters, and receptors in cancer cells. Curcumin also uplifted the SDH expression, which was inhibited in high glucose condition. Taken together, the findings of the present investigation first time demonstrate the ability of curcumin against high glucose-induced chemoresistance, along with its molecular mechanism. This will have implication in therapeutic management of malignancies in diabetic conditions.

Sensitive and specific detection of micrometastasis of hepatic carcinoma in peripheral blood by immunomagnetic nanobeads polymerase chain reaction

This study aims to determine the value of miR-133a-3p in diagnosing micrometastasis of hepatic carcinoma (HCC) from peripheral blood (PB) samples and dissecting the molecular mechanism (MM) of micrometastasis. We selected 70 patients with micrometastasis of HCC from our hospital between August 2014 to August 2020 for the research (Res) group and enrolled 55 patients with HCC but without micrometastasis in the control (Con) group. We collected PB samples from each participant and quantified miR-133a-3p in each sample using immunomagnetic nanobeads (IMNBs)-based PCR and RT-PCR. In contrast to the Con group, the Res group presented a significant down-regulation of miR-133a-3p in PB. The IMNBs and RT-PCR showed that miR-133a-3p exhibited the area under the curves (AUCs) of 0.882 and 0.845, specificities of 81.82% and 74.55%, and sensitivities of 85.71% and 88.57%, respectively. Due to its higher specificity and sensitivity, IMNBs were utilized. IMNBs were then used to quantify miR-133a-3p in HCC cells. Additionally, we explored the association of miR-133a-3p with PAF; miR-133a-3p was inversely correlated with AFP (r =−0.614; P &lt;0.001). miR-133a-3p’s targeting association with MMP15 and the corresponding MM was verified and analyzed. The up-regulation of miR-133a-3p levels inhibited the migration and invasion of HCC cells, while its down-regulation yielded the opposite effect. Moreover, miR-133a-3p negatively regulated the protein level of MMP15, the migration and invasion capacity of HCC cells was greatly impacted. In short, miR-133a-3p decreased in HCC micrometastasis. The detection of miR-133a-3p by IMNBs is both specific and sensitive in diagnosing the micrometastasis. miR-133a-3p is of enormous value in diagnosing HCC micrometastasis from PB samples, and its up-regulation can inhibit MMP15 and hinder HCC metastasis.

Long non-coding RNA XIST accelerates hepatic carcinoma progression by targeting the microRNA-320a/PIK3CA axis.

The aim of the present study was to reveal the new molecular mechanism of long non-coding (lnc)RNA XIST in the development of hepatic carcinoma. A total of 69 patients with hepatic carcinoma were included. Hepatoma cell lines (SUN449), hepatoblastoma cell line (HepG2, Huh-6), liver cancer cell line (HepG2) and transformed human liver epithelial-2 cells (THLE-2) were used in the present study. A total 3 short hairpin RNA (sh)-lncRNA XIST sequences, overexpression vector (oe)-lncRNA XIST, microRNA (miR)-320a mimic, miR-320a inhibitor, PIK3CA inhibitor, and their corresponding controls were transfected in hepatic carcinoma cells. Reverse transcription-quantitative polymerase chain reaction was conducted to detect lncRNA-XIST, miR-320a and PIK3CA expression. Cell Counting Kit-8 assay and flow cytometry were undertaken to measure proliferation and apoptosis. Cell invasion and migration were detected by Transwell assays. Moreover, the binding of lncRNA XIST, PIK3CA and miR-320a were verified by luciferase reporter experiment and pull-down assay. Finally, a rescue assay was processed to confirm the effect of lncRNA-XIST, miR-320a and PIK3CA in the aforementioned processes. lncRNA XIST was highly expressed in hepatic carcinoma tissues and cells. The survival rate was significantly lower in the highly expressed lncRNA XIST group. shlncRNA XIST attenuated cell proliferation, invasion and migration, while increasing the apoptosis of hepatic carcinoma cells. The lncRNA XIST negatively targeted miR-320a, and miR-320a negatively regulated the expression of PIK3CA. The miR-320a mimic and PIK3CA inhibitor could recover the effect of oe-lncRNA in terms of the proliferation, invasion, migration and apoptosis of hepatic carcinoma cells. lncRNA XIST accelerates hepatic carcinoma progression by targeting the miR-320a/PIK3CA axis, which might provide the theoretical basis for the potential targeted therapy of hepatic carcinomas.

Tumor Cell-Derived Exosomal Circ-0072088 Suppresses Migration and Invasion of Hepatic Carcinoma Cells Through Regulating MMP-16.

Background: Tumor-derived exosomes (EXOs), commonly differentially expressed in circular RNAs, have been shown to be crucial determinants of tumor progression and may regulate the development and metastasis of hepatic carcinoma (HCC).Methods: Possibly differentially expressed circRNAs in patients with HCC were screened out from the Gene Expression Omnibus (GEO). EXOs were isolated from the culture medium of HCC cells and plasma of patients with HCC, followed by characterization by transmission electron microscope, NanHCCight, and western blotting. Additionally, RNA immunoprecipitation and luciferase reporter gene assays were carried out to explore the molecular mechanism of hsa_circRNA_103809 (circ-0072088) in HCC cells.Results: The screening results showed that circ-0072088 was highly expressed in patients with HCC, and its increase indicated unfavorable prognosis of patients according to quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Additionally, circ-0072088 was mainly secreted by HCC cells via EXOs in plasma of such patients, and its high level in plasma EXOs was closely associated with tumor node metastasis (TNM) staging and tumor size. Moreover, HCC-secreted EXOs mediated the degradation of miR-375 via circ-0072088 and upregulated MMP-16, thus suppressing the metastasis of HCC.Conclusion: Upregulated in patients with HCC, circ-0072088 may be an index for diagnosis and prognosis of HCC. In addition, HCC-derived EXOs coated with circ-0072088 might be a treatment for HCC, with the ability to inhibit the metastasis of HCC cells.

Alginate-azo/chitosan nanocapsules in vitro drug delivery for hepatic carcinoma cells: UV-stimulated decomposition and drug release based on trans-to-cis isomerization

In this study, a nanocapsule (AL-azo/CH) was prepared with the anionic alginate-azo (AL-azo) and cationic chitosan (CH) via layer-by-layer method. Doxorubicin hydrochloride (DOX), an anticancer drug, was entrapped inside the AL-azo nanocapsules to form the DOX-loaded nanocapsules (DOX/AL-azo/CH). When the DOX/AL-azo/CH nanocapsules were irradiated with 365-nm light, the electrostatic attraction between the layers would be weakened as the trans-to-cis isomerization of AL-azo, which would lead to the UV-responsive decomposition and drug-release. Furthermore, cellular experiments showed that DOX/AL-azo/CH nanocapsules could be endocytosed by the HepG2 cells, and the confocal laser scanning microscope images showed that the DOX fluorescence intensity became stronger with the prolonging of irradiation time, indicating that the intracellular DOX-release could be controlled by UV irradiation. The AL-azo/CH nanocarriers were UV-triggered decomposition and drug-release, which stepped further towards the next-generation of nano-therapeutics with spatial and temporal external control in the field of polysaccharide.

Primary Hepatic Squamous Cell Carcinoma With High Microsatellite Instability Shows Good Response to Programmed Cell Death 1 Inhibitor as Adjuvant Therapy

Primary hepatic squamous cell carcinoma (SCC) is a rare, highly aggressive liver cancer that is associated with intrahepatic stone, liver cirrhosis, hepatic cyst, and Caroli's disease. At present, there are no settled therapy guidelines for primary hepatic SCC. Patients with successful surgical resection have a tumor-free survival of approximately 6 to 9 months.(1,2) Immune checkpoint inhibitors (ICIs) are a promising treatment for multiple tumor types, with significant efficacy and manageable toxicity.(3).

Dielectrophoresis-based discrimination of hepatic carcinoma cells following treatment with cytotoxic agents

Lack of advancement in detection of abnormal liver cells is a major drawback in hepatocellular carcinoma (HCC) that could results in late diagnosis. This study aims to discriminate the malignant cells from the normal counterparts, and apoptotic cells from viable cells using a microfluidic dielectrophoresis (DEP)-based technology. The discrimination of the viable and non-viable HCC cells was conducted upon treatment with plant-based cytotoxic agent konjac glucomannan (KGM). DEP analyses of human normal liver (WRL68) cells showed slight positive-DEP effect while liver cancer (HepG2) cells was highly negative. This broad dielectric difference is due to the tumorigenic alterations in HepG2 cells. Exposure to cytotoxic agents showed a significant shift from negative-DEP to positive-DEP, indicating apoptosis-induced reduction in membrane negativity. The results indicate the feasibility of DEP method in cancer screening.