摘要
目的:探讨新合成黄腐酚类似物联合顺铂对宫颈癌Hela细胞化疗敏感性的影响及其机制。方法:以不同浓度(5、7.5、15、20μmol/L)黄腐酚类似物处理宫颈癌Hela细胞和正常MRC-5细胞48 h后,MTT实验检测细胞增殖活力并计算出黄腐酚类似物对2种细胞的半数抑制浓度(IC_(50));采用MTT实验进一步观察IC_(50)最低的黄腐酚类似物联合顺铂对Hela和MRC-5细胞增殖活力的影响,采用流式细胞仪检测Hela细胞周期和凋亡情况,Western blot法检测Hela细胞中凋亡相关蛋白表达变化。结果:黄腐酚类似物a8、a13、b11和b12对宫颈癌Hela细胞增殖均有一定的抑制作用,且a13的IC50值最小;另外,这4种浓度的黄腐酚类似物对正常MRC-5细胞有轻微的抑制作用,且a13的IC50值最大。与对照组比较,顺铂组、a13组、顺铂+a13组中正常MRC-5细胞存活率差异均无统计学意义(P<0.05),但顺铂组、a13组和顺铂+a13组中宫颈癌Hela细胞存活率、G2/M期细胞百分比和B淋巴细胞瘤-2基因(Bcl-2)蛋白表达水平均明显降低,而G0/G1期细胞百分比、细胞凋亡率和细胞中细胞色素C(Cyt-c)、Bcl-2关联X蛋白(Bax)、活化的半胱氨酸天冬氨酸蛋白酶3(Cleaved Caspase-3)、活化的半胱氨酸天冬氨酸蛋白酶9(Cleaved Caspase-9)蛋白表达水平均明显升高,且顺铂+a13组中上述指标变化幅度明显大于顺铂组、a13组(P<0.05)。结论:黄腐酚类似物与顺铂联合可协同抑制宫颈癌Hela细胞增殖,表现良好的化疗增敏效果,其作用机制可能与阻滞细胞周期进程和调控凋亡相关蛋白表达促进细胞凋亡有关。
Objective:To investigate the effect of newly synthesized xanthohumol analogues combined with cisplatin on the chemosensitivity of cervical cancer Hela cells and its mechanism.Methods:Cervical cancer Hela cells and normal MRC-5 cells were treated with xanthohumol analogs at different concentrations(5,7.5,15,20μmol/L)for 48 h.The MTT assay was used to detect the cell proliferation activity and calculate the half inhibitory concentration(IC50)of xanthohumol analogues on two kinds of cells.MTT assay was used to further observe the effect of xanthohumol analogue with the lowest IC50 combined with cisplatin on the proliferation of Hela and MRC-5 cells.Hela cell cycle and apoptosis were detected by flow cytometry.The expression of apoptosis related proteins in Hela cells was detected by Western blot.Results:Xanthohumol analogues a8,a13,b11 and b12 had certain inhibitory effects on the proliferation of cervical cancer Hela cells,and the IC50 value of a13 was the lowest.In addition,the four xanthohumol analogues had a slight inhibitory effect on normal MRC-5 cells,and the IC50 value of A13 was the largest.Compared with the control group,there were no significant differences in the survival rate of normal MRC-5 cells in cisplatin group,a13 group and cisplatin combined with a13 group(P<0.05),but the survival rate of cervical cancer Hela cells,the percentage of G2/M phase cells and the expression level of Bcl-2 protein in cisplatin group,a13 group and cisplatin combined with a13 group were significantly reduced,while the percentage of G0/G1 phase cells,the cell apoptosis rate and cytochrome c(Cyt-c),B lymphoma-2(Bcl-2)associated X protein(Bax),activated caspase-3(Cleaved Caspase-3)and activated caspase-9(Cleaved Caspase-9)protein expression levels increased significantly,and the change range of the above indexes in cisplatin combined with a13 group was significantly greater than that in cisplatin group and a13 group(P<0.05).Conclusion:The combination of xanthohumol analogue and cisplatin can synergistically inhibit the proliferation of cervical cancer Hela cells and show a good chemosensitization effect.Its mechanism may be related to blocking the process of cell cycle,regulating the expression of apoptosis related proteins and promoting apoptosis.
作者
王慧
朱婕曼
刘树英
亢延飞
陈江平
WANG Hui;ZHU Jie-man;LIU Shu-ying;KANG Yan-fei;CHEN Jiang-ping(Department of Obstetrics and Gynecology,The First Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei,075000,China;Hebei North University,Zhangjiakou,Hebei,075000,China)
出处
《现代生物医学进展》
CAS
2022年第13期2441-2446,共6页
Progress in Modern Biomedicine
基金
河北省医学科学研究重点课题计划青年科技项目(20180815)。
关键词
新合成黄腐酚类似物
宫颈癌
顺铂
细胞凋亡
化疗敏感性
Newly synthesized xanthohumol analogues
Cervical cancer
Cisplatin
Cell apoptosis
Chemosensitivity
