Chidamide induces apoptosis of colon cancer HCT-15 cells through mitochondrial apoptosis pathway

doi:10.3969/j.issn.1000-1565.2022.02.009

Abstract

Abstract: The inhibitory effect and mechanism of Chidamide on the proliferation of colon cancer cell line HCT-15 were studied. HCT-15 were treated with different concentrations of Chidamide, and cell proliferation and drug sensitivity were detected by CCK-8 method; The ability of cell clone formation in vitro was detected by plate clone formation assay. Apoptosis was detected by flow cytometry. The cell cycle was detected by EdU experiment, the expression level of acetylated histone, mitochondrial apoptosis-related proteins, and cell cycle-related proteins were detected by Western blot. The results show that Chidamide inhibited the proliferation of HCT-15 cells in a concentration and time-dependent manner, weakened the ability- DOI:10.3969/j.issn.1000-1565.2022.02.009西达本胺通过线粒体凋亡途径诱导结肠癌HCT-15细胞凋亡赵琳珊^1,2,李玉苗¹,李楠¹,贾友超¹,王晓芳¹,韩强¹,臧爱民¹(1.河北大学附属医院肿瘤内科,河北省肿瘤放化疗机制与规程研究重点实验室,河北保定 071000;2.河北大学临床医学院,河北保定 071000)摘要:研究西达本胺(Chidamide)对结肠癌细胞系HCT-15的增殖抑制作用及机制. 以不同浓度西达本胺处理HCT-15细胞,CCK-8法检测细胞增殖情况及细胞的药物敏感性;平板克隆形成实验检测细胞体外克隆形成能力;流式细胞术检测细胞凋亡;EdU实验检测细胞增殖周期;Western blot检测乙酰化组蛋白、线粒体凋亡途径相关蛋白、细胞周期相关蛋白表达水平的变化. 结果表明:西达本胺抑制HCT-15细胞增殖呈浓度和时间依赖性,细胞体外克隆形成能力减弱,凋亡增多,细胞分裂相明显减少、总周期变慢,乙酰化组蛋白H3和H4、线粒体介导的相关凋亡蛋白表达上调、p21、p27表达上调、CDK2、CyclinA2蛋白表达下调. 西达本胺可抑制HCT-15细胞增殖,通过线粒体途径诱导细胞凋亡并阻滞细胞周期. 关键词:西达本胺;结肠癌;乙酰化;线粒体凋亡途径中图分类号:R917 文献标志码:A 文章编号:1000-1565(2022)02-0164-07Chidamide induces apoptosis of colon cancer HCT-15 cells through mitochondrial apoptosis pathwayZHAO Linshan^1,2, LI Yumiao¹, LI Nan¹, JIA Youchao¹, WANG Xiaofang¹, HAN Qiang¹, ZANG Aimin¹(1. Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Department of Medical Oncology, Affiliated Hospital of Hebei University, Baoding 071000, China; 2. Clinical Medical College, Hebei University, Baoding 071000, China )Abstract: The inhibitory effect and mechanism of Chidamide on the proliferation of colon cancer cell line HCT-15 were studied. HCT-15 were treated with different concentrations of Chidamide, and cell proliferation and drug sensitivity were detected by CCK-8 method; The ability of cell clone formation in vitro was detected by plate clone formation assay. Apoptosis was detected by flow cytometry. The cell cycle was detected by EdU experiment, the expression level of acetylated histone, mitochondrial apoptosis-related proteins, and cell cycle-related proteins were detected by Western blot. The results show that Chidamide inhibited the proliferation of HCT-15 cells in a concentration and time-dependent manner, weakened the ability- 收稿日期:2021-11-19 基金项目:河北省政府资助临床医学优秀人才课题(361007);河北大学医学学科培育项目(2021B15) 第一作者:赵琳珊(1995—),女,河南安阳人,河北大学在读硕士研究生,主要从事肿瘤药理学研究. E-mail:13502155703@163.com 通信作者:臧爱民(1962—),女,河北保定人,河北大学附属医院教授,主要从事肿瘤生物学治疗方向研究. E-mail:booszam@sina.com韩强(1968—),女,河北保定人,河北大学附属医院主任医师,主要从事肿瘤生物学治疗方向研究. E-mail:hanqiang68716@alliyun.com第2期赵琳珊等:西达本胺通过线粒体凋亡途径诱导结肠癌HCT-15细胞凋亡of cell cloning in vitro, increased apoptosis, significantly reduced the image of cell division, and slowed down the total cycle. The results of western blot showed that acetylated histones H3, H4, mitochondria-mediated apoptosis-related proteins, p21, and p27 were up-regulated. Meanwhile, CDK2 and cyclin A2 were down-regulated. Chidamide could inhibit proliferation, induce apoptosis and block the cell cycle of HCT-15 cells.

Key words: Chidamide, colon cancer, acetylation, mitochondrial apoptosis pathway

CLC Number:

R917

ZHAO Linshan, LI Yumiao, LI Nan, JIA Youchao, WANG Xiaofang, HAN Qiang, ZANG Aimin. Chidamide induces apoptosis of colon cancer HCT-15 cells through mitochondrial apoptosis pathway[J]. Journal of Hebei University(Natural Science Edition), 2022, 42(2): 164-170.

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