槲皮素对索拉非尼耐药Hela细胞增殖、迁移、凋亡及自噬的研究  

Study of Quercetin on Proliferation, Migration, Apoptosis and Autophagy of Sorafenib-Resistant Hela Cells

作　　者：李珂莹 刘晨燕 马盼盼 王晴晴 潘治花 王至卓 姬国杰 胡焕焕 

机构地区：[1]新乡医学院三全学院生育力保存重点实验室,河南 新乡

出　　处：《临床医学进展》2024年第1期27-35,共9页Advances in Clinical Medicine

摘　　要：目的:探讨槲皮素(Quercetin, QU)联合索拉非尼(Solafenib)对索拉非尼耐药Hela细胞的作用及其机制。方法:MTT法测定不同浓度索拉非尼(0, 2.5, 5.0, 7.5, 10.0, 15.0, 20.0 µmol/L)对细胞的增殖的影响;细胞划痕实验检测各组细胞的迁移水平;PCR实验检测各组凋亡基因Bax、Bcl-2及自噬基因LC3-B、Beclin-1的表达水平;Western-blot (WB)检测细胞凋亡相关蛋白caspase-3的相对表达量。结果:随着药物浓度的增加,耐药细胞和亲本细胞的抑制率逐渐升高,且对亲本细胞的抑制率明显高于耐药细胞。联合用药组抑制耐药细胞的迁移率,并且联合用药组的Bax和LC3-B基因相对表达量降低,Bcl-2、Beclin-1基因相对表达量、Bax/Bcl-2的值以及caspase-3蛋白相对表达量升高,与空白对照组和索拉非尼组相比,联合用药组细胞凋亡显著升高。结论:槲皮素与索拉非尼联合用药是通过上调Bcl-2、Beclin-1、Bax/Bcl-2基因相对表达量、下调Bax、LC3-B基因相对表达量同时上调caspase-3蛋白相对表达量的途径,抑制耐药细胞的迁移率、促进耐药细胞凋亡、抑制细胞自噬,从而起到逆转耐索拉非尼Hela细胞耐药性的作用。Objective: To investigate the effect and mechanism of quercetin and sorafenib on soraf-enib-resistant Hela cells. Methods: The effects of sorafenib at different concentrations (0, 2.5, 5.0, 7.5, 10.0, 15.0, 20.0 µmol/L) were measured on cell proliferation by cell nicking assay;the expres-sion levels of apoptotic genes Bax, Bcl-2 and autophagy genes LC3-B, Beclin-1 by PCR;and the rela-tive expression of apoptosis related protein caspase-3 by Western-blot (WB). Results: With the in-crease of the drug concentration, the inhibition rate of the resistant cells and the parent cells was significantly higher than that of the resistant cells. The combination group inhibited the migration rate of resistant cells, and the relative expression of Bax and LC3-B genes, the relative expression of Bcl-2 and Beclin-1 genes, values of Bax/Bcl-2 and caspase-3 protein was increased and significantly increased apoptosis in the combination group compared with the blank control group and sorafenib group. Conclusion: The combination of quercetin and sorafenib regulates the relative expression of Bcl-2, Beclin-1, Bax/Bcl-2 genes, the down-regulation of the relative expression rate of caspase-3 protein, inhibits the mobility of resistant cells, promotes the apoptosis and autophagy, so as to re-verse the drug resistance of sorafenib-resistant Hela cells.

关 键 词：HELA细胞 索拉非尼 槲皮素 耐药 细胞凋亡 

分 类 号：R73[医药卫生—肿瘤]