新型塔斯品碱衍生物HMQ-T-B10诱导人结肠癌细胞LoVo凋亡作用及机制研究  

Study of Apoptosis-inducing Effects and Underlying Mechanism of New Taspine Derivative HMQ-T-B10 in Human Colorectal Carcinoma LoVo Cells

作　　者：雍素云 张丹[1] 周楠[1] 张鹏[1] 史先鹏 YONG Su-Yun;ZHANG Dan;ZHOU Nan;ZHANG Peng;SHI Xian-Peng(Department of Pharmacy,Shaanxi Provincial People's Hospital,Xi'an 710068,China)

机构地区：[1]陕西省人民医院药学部,陕西西安710068

出　　处：《药物生物技术》2024年第1期9-14,共6页Pharmaceutical Biotechnology

基　　金：陕西省中医药管理局中医药传承创新暨“秦药”重点科学研究项目(No.2021-02-zz-015);陕西省人民医院院内人才支持计划项目(No.2021JY-29);陕西省自然科学基金青年项目(No.2023-JC-QN-0936);陕西省自然科学基金(No.2022JM-605)。

摘　　要：探讨塔斯品碱衍生物HMQ-T-B10对人结肠癌LoVo细胞生长的影响及其诱导细胞凋亡的可能作用机制。采用MTT法、细胞克隆形成实验、Hoechst染色法、流式细胞术法检测低(2μmol/L)、中(4μmol/L)、高(8μmol/L)3种浓度HMQ-T-B10对LoVo细胞株增殖及凋亡的影响;Western-Blot法检测3种浓度HMQ-T-B10对Bcl-2、Mcl-1、Bax、Cyto-C、Cleaved caspase-3、Cleaved caspase-7蛋白表达水平的影响。MTT法结果显示HMQ-T-B10能明显抑制LoVo细胞的增殖,其半数抑制浓度(IC_(50))值为(7.9±1.1)μmol/L。细胞克隆形成实验表明3种浓度的HMQ-T-B10均可剂量依赖性抑制LoVo细胞增殖,Hoechst染色及流式细胞术显示HMQ-T-B10可剂量依赖性诱导LoVo细胞凋亡。Western-Blot结果显示4μmol/L及8μmol/L HMQ-T-B10可显著下调Bcl-2蛋白表达并增加Cyto-C表达,3种浓度的HMQ-T-B10均可显著抑制Mcl-1蛋白表达并升高Bax及Cleaved caspase-7表达,8μmol/L HMQ-T-B10可显著性增加Cleaved caspase-3表达。HMQ-T-B10可抑制LoVo细胞增殖,可能通过Bcl-2/Caspase通路诱导其凋亡。To investigate the inhibitory effects of taspine derivatives HMQ-T-B10 and the possible mechanism of inducing apoptosis on human colorectal carcinoma LoVo cells,MTT assay and cell clone formation assay were used to detect the effects of low(2μmol/L)concentration group,medium(4μmol/L)concentration group and high(8μmol/L)concentration group of HMQ-T-B10 on the proliferative of human colorectal carcinoma LoVo cell lines.Hoechst staining method and flow cytometry were used to detect the effects of low,medium and high concentrations group of HMQ-T-B10 on the apoptosis of human colorectal carcinoma LoVo cell lines.Western-Blot assay were used to detect the effects of three concentrations group of HMQ-T-B10 on the protein expression level of Bcl-2,Mcl-1,Bax,Cyto-C,Cleaved caspase-3 and Cleaved caspase-7.MTT assay showed that HMQ-T-B10 could significantly inhibit the proliferation of human colorectal carcinoma LoVo cells lines with half inhibitory concentration(IC_(50))value of(7.9±1.1)μmol/L,and the cell clone formation assay demonstrated that all the three concentrations group of HMQ-T-B10 could dose-dependently inhibit the proliferation of human colorectal carcinoma LoVo cells.Hoechst staining method and flow cytometry showed that all the three concentrations group of HMQ-T-B10 could dose-dependently induce apoptosis of human colorectal carcinoma LoVo cells.Western-Blot results showed that both 4μmol/L and 8μmol/L HMQ-T-B10 concentration group could significantly down-regulate the expression level of Bcl-2 protein and increase the expression level of Cyto-C protein,and that all the three concentrations of HMQ-T-B10 group could significantly inhibit the expression level of Mcl-1 protein and elevate the expression level of Bax protein and Cleaved caspase-7 protein,and 8μmol/L HMQ-T-B10 concentration group could significantly increas the Cleaved caspase-3 protein expression level.HMQ-T-B10 inhibited the proliferation of human colorectal carcinoma LoVo cells and probably induced apoptosis through the Bcl-2/Caspase

关 键 词：塔斯品碱 HMQ-T-B10 人结肠癌LoVo细胞 增殖 凋亡 Bcl-2 含半胱氨酸的天冬氨酸蛋白水解酶 

分 类 号：R735.35[医药卫生—肿瘤]