天花粉蛋白对宫颈癌HeLa细胞顺铂化疗增敏作用  

Effect of Trichosanthin on Chemosensitivity of Cervical Cancer HeLa Cells to Cisplatin

作　　者：谭顺梓 向珺昱 夏玉桦 尤程程[1,2] 黄利鸣[1,2] 黄益玲[1,2] TAN Shunzi;XIANG Junyu;XIA Yuhua;YOU Chengcheng;HUANG Liming;HUANG Yiling(Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy,Medical College,China Three Gorges University,Yichang 443002,China;Clinial Medical Department of China Three Gorges University,Yichang 443002,China;Department of Gynecology,Enshi Central Hospital,Hubei Province,Enshi 445000,China)

机构地区：[1]三峡大学医学院肿瘤微环境与免疫治疗湖北省重点实验室,宜昌443002 [2]三峡大学临床医学系,宜昌443002 [3]湖北省恩施市中心医院妇科,恩施445000

出　　处：《医药导报》2023年第7期953-958,共6页Herald of Medicine

基　　金：国家自然科学基金面上项目(81374024);宜昌市医疗卫生科研项目(A22-2-070,A21-2-048);肿瘤微环境与免疫治疗湖北省重点实验室(三峡大学)开放基金资助项目(2021KZL03)。

摘　　要：目的观察天花粉(TCS)联合顺铂对宫颈癌HeLa细胞的化学治疗(化疗)增敏作用,并探讨其作用机制。方法细胞计数检测试剂盒(CCK8)法检测TCS、顺铂单独或联合用药对宫颈癌HeLa细胞增殖的影响;CompuSyn软件分析TCS联合顺铂的联合用药指数(CI值);细胞划痕实验与Transwell法检测药物对细胞迁移的影响;流式细胞术检测药物对细胞凋亡的影响;蛋白印迹法检测药物对HeLa细胞凋亡相关蛋白表达水平的影响。结果TCS与顺铂均能抑制宫颈癌HeLa细胞增殖,TCS+顺铂抑制作用更强,TCS对顺铂增敏指数为3.04;不同浓度TCS联合顺铂作用HeLa细胞48 h后,CI值均<1,且具有浓度依赖性(P<0.05);细胞划痕实验与Transwell法实验中,TCS+顺铂较TCS或顺铂单独给药能更明显抑制HeLa细胞迁移(P<0.05);流式细胞术中,与TCS或顺铂单独给药相比,TCS+顺铂可增加HeLa细胞凋亡比例(P<0.05);蛋白印迹实验中,与TCS或顺铂相比,TCS+顺铂可上调促凋亡蛋白Bax、c-PARP表达,下调凋亡抑制蛋白Bcl-2表达(P<0.05)。结论TCS+顺铂对抑制宫颈癌HeLa细胞生长具有协同效应,TCS对顺铂化疗有增敏作用,其机制可能与TCS联用后促进HeLa细胞凋亡及抑制细胞迁移有关。Objective To determine the chemosensitization effect of trichosanthin(TCS)and cisplatin on cervical cancer HeLa cells,and preliminarily explore its mechanism.Methods The effects of TCS and cisplatin alone or in combination on the proliferation of cervical cancer HeLa cells were detected by CCK8 assay.The combination index(CI)of TCS and cisplatin was detected by CompuSyn software.The effects of drugs on cell migration were detected by wound healing assay and transwell assay.The effect of drugs on cell apoptosis was detected by flow cytometry.The effect of drugs on the expression levels of apoptosis-related proteins in HeLa cells was analyzed by Western blotting.Results TCS and cisplatin alone could inhibit the proliferation of cervical cancer HeLa cells,and the combination of TCS and cisplatin showed more potent inhibition.The sensitization index of TCS to cisplatin was 3.04.The CI values of TCS and cisplatin after 48 h treatment were all less than 1 in a concentration-dependent manner(P<0.05).Cell scratch test and Transwell method showed that the combination group could significantly inhibit the migration of HeLa cells compared with the single drug group(P<0.05).Flow cytometry results showed that the apoptosis rate of HeLa cells increased in the combination therapy group compared with the single therapy group(P<0.05).Western blotting assay showed that compared with the single drug group,the combination drug up-regulated the expression of pro-apoptotic proteins Bax and C-PARP,and down-regulated the expression of apoptotic inhibitory protein Bcl-2(P<0.05).Conclusions TCS combined with cisplatin has a synergistic effect on inhibiting the growth of cervical cancer HeLa cells.TCS can sensitize HeLa cells to cisplatin by chemotherapy,and the mechanism may be related to the increment of HeLa cell apoptosis and inhibition of migration.

关 键 词：天花粉蛋白 顺铂 宫颈癌 化学治疗增敏 

分 类 号：R286[医药卫生—中药学] R965[医药卫生—中医学]