Effect of gallic acid in increasing the chemosensitivity of hepatocellular carcinoma HepG2 cells to sorafenib
Journal Title: Journal of Clinical Hepatology - Year 2025, Vol 41, Issue 2
Abstract
[Objective] To investigate the chemosensitization effect of gallic acid （GA） combined with sorafenib （Sora） on hepatocellular carcinoma HepG2 cells and related mechanisms. [Methods] HepG2 cells were randomly divided into control group， GA group， Sora group， and GA+Sora group. CCK8 assay was used to measure cell viability； CompuSyn software was used to analyze combination index （CI）； colony formation assay was used to evaluate the colony formation ability of cells； flow cytometry was used to measure cell apoptosis； wound healing assay and Transwell chamber assay were used to observe the migration and invasion abilities of cells； Western Blot was used to measure the expression matrix metalloproteinase 2 （MMP-2）， matrix metalloproteinase 9 （MMP-9）， and apoptosis-related proteins. HepG2 cells were subcutaneously inoculated into the lower right back of mice， and 6 days later， the mice were divided into control group， GA group， Sora group， and GA+Sora group. Tumor size and body weight were measured once a week， and drug intervention was performed for 21 days. Then the nude mice were sacrificed， and tumor weight was measured. A one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. [Results] The mean IC50 values of GA and Sora for the treatment of HepG2 cells for 48 hours were 123.47±5.16 μmol/L and 9.87±0.98 μmol/L， respectively， and when Sora was combined with 70 μmol/L GA （IC30）， IC50 decreased to 2.06±0.35 μmol/L； the CI value was<1 for Sora at different concentrations combined with 70 μmol/L GA. The number of cell colonies was 234.0±20.4， 147.0±12.1， 129.3±13.3， and 73.0±7.6， respectively， in the four groups， and the GA+Sora group had a significantly lower number of cell colonies than the control group， the GA group， and the Sora group （all P<0.05）. After 48 hours of treatment， the cell apoptosis rate was 1.98%±0.29%， 15.17%± 1.56%， 18.65%±1.48%， and 34.60%±5.36%， respectively， in the four groups， and the GA+Sora group had a significantly higher cell apoptosis rate than the control group， the GA group， and the Sora group （all P<0.05）. After 24 hours of treatment， the cell migration rate was 55.59%±5.08%， 29.34%±4.36%， 21.80%±5.16%， and 6.47%±2.75%， respectively， in the four groups， and the GA+Sora group had a significantly lower cell migration rate than the control group， the GA group， and the Sora group （all P<0.05）. After 48 hours of treatment， the number of transmembrane cells was 223.7±13.0， 168.3±10.9， 155.3±29.1， and 62.7±19.7， respectively， in the four groups， and the GA+Sora group had a significantly lower number of transmembrane cells than the control group， the GA group， and the Sora group （all P<0.05）. Compared with the control group， the GA group， the Sora group， and the GA+Sora group had significant reductions in the protein expression levels of MMP-2， MMP-9， and Bcl-2 （all P<0.05） and significant increases in the protein expression levels of Bax and cleaved caspase-3 （all P<0.05）. Compared with the control group， the GA， Sora， and GA+Sora groups had significant reductions in tumor volume and weight （all P<0.05）， and compared with the Sora group， the GA+Sora group had significant reductions in tumor volume and weight in nude mice （both P<0.05）. [Conclusion] GA can increase the sensitivity of HepG2 cells to Sora chemotherapy， possibly by promoting cell apoptosis and inhibiting cell migration and invasion after combination with Sora.
Authors and Affiliations
Baikun LIU, Zhiru WANG, Wenjing ZHAO
Keywords
Related Articles
- EP ID EP768442
- DOI 10.12449/JCH250215
- Views 4
- Downloads 0
Current status of ex vivo liver resection and autotransplantation in treatment of benign liver lesions
Benign liver lesions mainly include hepatic hemangioma， focal nodular hyperplasia of the liver， hepatocellular adenoma， and hepatic angiomyolipoma. Hepatic alveolar echinococcosis is a type of parasitic disease， and...
Hepatitis flare and treatment in postpartum women with chronic hepatitis B virus infection
Hepatitis flare can happen in postpartum women with chronic hepatitis B virus （HBV） infection due to the changes in immune function and hormone levels. In order to delay disease progression in parturients and ensure th...
Efficacy of des-γ-carboxy-prothrombin in the diagnosis of hepatocellular carcinoma and its association with the clinical features of hepatocellular carcinoma
[Objective] To investigate the value of des-γ-carboxy-prothrombin （DCP） in hepatocellular carcinoma （HCC）. [Methods] A retrospective analysis was performed for the clinical data of 179 HCC patients who were admitted...
Effect of sorafenib and donafenib on the pharmacokinetics of ertugliflozin in rats
[Objective] To investigate the effect of sorafenib and donafenib on the pharmacokinetics of ertugliflozin in rats， and to provide a theoretical basis for drug combination in clinical practice. [Methods] A total of 24 ma...
The genetic association between nonalcoholic fatty liver disease and type 2 diabetes mellitus in different body mass index categories： A bidirectional Mendelian randomization study
[Objective] To investigate the genetic association between nonalcoholic fatty liver disease （NAFLD） and type 2 diabetes mellitus （T2DM） using bidirectional two-sample Mendelian randomization （MR）， as well as the c...