Effect of sorafenib induced apoptosis and autophagy on drug resistance in HeLa cells
10.16352/j.issn.1001-6325.2024.04.0467
- VernacularTitle:索拉菲尼诱导的细胞凋亡和自噬对HeLa细胞耐药性的影响
- Author:
Kaifei YANG
1
;
Jingge ZHU
;
Yangyang ZHANG
;
Junguo ZHAO
;
Yuyue GAO
;
Huanhuan HU
;
Guojie JI
Author Information
1. 新乡医学院三全学院生命科学技术学院,河南 新乡 453000
- Keywords:
sorafenib;
cervical cancer;
cell drug resistance;
apoptosis;
autophagy;
cell cycle
- From:
Basic & Clinical Medicine
2024;44(4):467-473
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effect of sorafenib on HeLa cell proliferation by inducing cell apoptosis and autophagy and its impact on drug resistance.Methods The drug-resistant cell strains were constructed through in-termittent induction method,with concentrations of 0,2.5,5.0,7.5,10.0,15.0,20.0 μmol/L.HeLa cells were incubated with increasing concentrations of sorafenib with each concentration for 1 week.The drug-resistant cell strains with stable passages were collected.MTT assay was used to detect the effect of sorafenib on cell prolifer-ation.Cell cycle distribution was analyzed by flow cytometry.The change in the expression of drug-resistant and ap-optotic genes in the parents and drug-resistant cell strains under different drug concentrations was examined by semi-quantitative PCR.The changes of apoptotic related marker proteins LC3-Ⅰ and LC3-Ⅱ were detected by Westernblot.Results Stable drug-resistant strains were successfully obtained;Drug-treated cells were more blocked in the G1 phase.In drug-resistant cells,the expression of apoptosis suppressor gene Bcl-2 was significantly decreased and the apoptotic gene Bax as well as the drug-resistant genes were all significantly increased(P＜0.05).The LC3-Ⅱ/LC3-Ⅰ ratio of drug-resistant cells was significantly higher than that of parent cells(P＜0.05).Conclusions Sorafenib may block the cell cycle,suppress malignant cell proliferation and promote autophage.On one hand,autophagy participates in the development of cell drug resistance and promotes cell survival.On the other hand,drug-induced autophagy may activate some of apoptotic signaling pathway in drug-resistant cells and promote the reversal of cell drug resistance.
