辣椒素经内质网应激反应途径诱导K562/ADM耐药细胞凋亡

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (8): 856-860.

辣椒素经内质网应激反应途径诱导K562/ADM耐药细胞凋亡

侯娟娟, 陈静, 易娟, 高丽丽, 魏虎来

兰州大学基础医学院,甘肃省新药临床前研究重点实验室,兰州 730000,甘肃

收稿日期:2010-05-30 修回日期:2010-07-10 出版日期:2010-08-26 发布日期:2020-09-17
通讯作者: 魏虎来,男,教授,博士研究生导师,研究方向:细胞分子生物学。Tel: 0931- 8915082 E-mail: weihulai@lzu.edu.cn
作者简介:侯娟娟,女,硕士研究生,研究方向:生物化学与分子生物学。Tel: 0931-8915391 E-mail: houjj08@lzu.cn
基金资助:
甘肃省科技支撑计划项目(1011FKCA145);甘肃省新药临床前研究重点实验室(GSKFKT-0701);甘肃省天然药物重点实验室(0804)开放基金资助项目

Capsaicin induces endoplasmic reticulum stress-related apoptosis in drug-resistant K562/ADM cells

HOU Juan-juan, CHEN Jing, YI Juan, GAO Li-li, WEI Hu-lai

School of Basic Medical Science, Lanzhou University, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou 730000, Gansu, China

Received:2010-05-30 Revised:2010-07-10 Online:2010-08-26 Published:2020-09-17

摘要/Abstract

摘要： 目的: 研究辣椒素(capsaicin)是否经内质网途径诱导耐药性白血病K562/ADM细胞凋亡。方法: 以耐药性白血病K562/ADM细胞为靶细胞,采用MTT比色法测定细胞增殖活性;细胞形态学和AnnexinV/PI双染色法检测细胞凋亡,电镜观察凋亡细胞内质网形态结构变化;实时定量RT-PCR检测GRP78 mRNA的表达;Western blot 法检测GRP78蛋白的表达。结果: 不同浓度的辣椒素显著抑制K562/ADM细胞的增殖活性,20、50 μmol/L辣椒素诱导后K562/ADM细胞出现典型的凋亡形态学改变,细胞凋亡率明显增高,分别为39.67%和41.78%。辣椒素诱导凋亡过程中,K562/ADM细胞出现内质网明显扩张和脱颗粒现象,GRP78 mRNA的表达增高,GRP78蛋白的表达量分别增高1.5和2.2倍,随时间延长有所降低。结论: 辣椒素可能通过内质网应激反应性途径诱导K562/ADM细胞发生凋亡。

关键词: 辣椒素, K562/ADM细胞, 内质网应激, 凋亡

Abstract: AIM: To investigate whether capsaicin induces apoptosis in drug-resistant leukemia K562/ADM cells mediated by endoplasmic reticulum stress-related pathway.METHODS: The drug-resistant leukemia K562/ADM cells were used as the target cells. The cell proliferating activity was assessed with MTT colorimetric assay. The apoptosis of K562/ADM cells was identified by double staining of FITC-Annexin V and propidium iodide (PI) and the cellular morphology. The ultrastructure of the cells and endoplasmic reticulum were observed by transmission electron microscopy. The expression of GRP78 gene mRNA and protein were analyzed by real-time reverse transcription-polymerase chain reaction(RT-PCR) and Western blotting, respectively.RESULTS: Capsaicin of different concentrations markedly inhibited the proliferation of K562/ADM cells and also induced the cells to apoptosis. After the treatment with 20 and 50 μmol/L capsaicin for 48 h, K562/ADM cells showed the typical morphological characteristics of apoptosis, and the apoptotic rate of the cells increased to 39.67% and 41.78%, respectively. During the apoptotic process of K562/ADM cells induced with capsaicin, the endoplasmic reticulum exhibited obvious expansion and degranulation. The expression of GRP78 gene mRNA of K562/ADM cells increased and then decreased slightly, the expression of GRP78 protein increased by 1.5 and 2.2 times respectively, and gradually reduced with the inducing time.CONCLUSION: Capsaicin may induce drug-resistant K562/ADM cells to apoptosis via endoplasmic reticulum stress-mediated pathway.

Key words: Capsaicin, K562/ADM cells, Endoplasmic reticulum stress, Apoptosis

中图分类号:

R965.2

侯娟娟, 陈静, 易娟, 高丽丽, 魏虎来. 辣椒素经内质网应激反应途径诱导K562/ADM耐药细胞凋亡[J]. 中国临床药理学与治疗学, 2010, 15(8): 856-860.

HOU Juan-juan, CHEN Jing, YI Juan, GAO Li-li, WEI Hu-lai. Capsaicin induces endoplasmic reticulum stress-related apoptosis in drug-resistant K562/ADM cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(8): 856-860.

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