文章摘要

苦参碱抑制 Nrf2 诱导的 Annexin A4 表达改善非小细胞肺癌对顺铂耐药

作者: 1刘冬, 2周伟, 3高晓博, 4王小霞, 5郭舜, 5石磊, 5张松
1 空军军医大学唐都医院肿瘤科,西安 710038
2 中国人民解放军第四五一医院医学工程科,西安 710054
3 中国人民解放军第三医院药剂科,陕西 宝鸡 721004
4 空军军医大学唐都医院皮肤科,西安 710038
5 空军军医大学唐都医院药剂科,西安 710038
通讯: 张松 Email: zhangsong801101@163.com
DOI: 10.3978/j.issn.2095-6959.2019.03.001
基金: 陕西省重点研发计划 (2017SF-136);陕西省自然科学基础研究计划 (2017JM8136)。

摘要

目的:探讨苦参碱对非小细胞肺癌(non-small lung cancer cell,NSCLC)顺铂耐药性的逆转作用及其机制。方法:MTT法检测细胞存活率;采用试剂盒检测细胞乳酸脱氢酶及caspase-3活性,考察核因子E-2-相关因子2(nuclear factor-E2-related factor,Nrf2)激动剂对NSCLC细胞凋亡及膜连蛋白A4(Annexin A4)表达的影响,同时考察苦参碱对NSCLC顺铂耐药的改善作用及对Nrf2/Annexin A4的调控作用。结果:使用Nrf2激动剂后,NSCLC细胞顺铂耐药显著,顺铂耐药细胞存活率较普通肺癌细胞显著升高,凋亡率显著降低,Annexin A4表达明显升高,而苦参碱可以显著抑制Nrf2诱导的Annexin A4表达,提高细胞对顺铂的敏感性,促进细胞凋亡发生。结论:苦参碱对人NSCLC顺铂耐药细胞株顺铂耐药性有改善作用,其机制可能与调节Nrf2/Annexin A4有关。
关键词: 非小细胞肺癌;顺铂;核因子E-2-相关因子2;膜连蛋白A4;苦参碱

Matrine inhibits Nrf2 induced Annexin A4 expression and improves cisplatin resistance in non-small cell lung cancer

Authors: 1LIU Dong, 2ZHOU Wei, 3GAO Xiaobo, 4WANG Xiaoxia, 5GUO Shun, 5SHI Lei, 5ZHANG Song
1 Department of Oncology, Tangdu Hospital, Air Force Medical University, Xi’an 710038
2 Department of Medical Engineering, 451 Hospital of PLA, Xi’an 710054
3 Department of Pharmacy, Third Hospital of the People’s Liberation Army, Baoji Shaanxi 721004
4 Department of Dermatology, Tangdu Hospital, Air Force Military Medical University, Xi’an 710038
5 Department of Pharmacy, Tangdu Hospital, Air Force Military Medical University, Xi’an 710038, China

CorrespondingAuthor: ZHANG Song Email: zhangsong801101@163.com

DOI: 10.3978/j.issn.2095-6959.2019.03.001

Foundation: This work was supported by Shaanxi Key Research and Development Program (2017SF-136) and Basic Research Program of Natural Science in Shaanxi Province (2017JM8136), China.

Abstract

Objective: To investigate the reversal effect of Matrine on cisplatin-resistant non-small cell lung cancer (NSCLC) cells and its mechanism. Methods: MTT assay was used to detect cell viability, lactate dehydrogenase (LDH) and caspase-3 (caspase-3) activity, and Nrf2 agonists were given to investigate the effects of Nrf2 on apoptosis and Annexin A4 expression in NSCLC cells. Matrine was also given to investigate its effect on cisplatin resistance and regulation of Nrf2/Annexin A4 in NSCLC. Results: MTT assay showed that Nrf2 agonist significantly inhibited the cisplatin resistance of NSCLC cells, the survival rate of cisplatin-resistant NSCLC cells was significantly higher than that of normal lung cancer cells, the apoptosis rate was significantly decreased, the expression of Annexin A4 was significantly increased, while matrine significantly inhibited Nrf2-induced Annexin A4 expression, and significantly increased the cisplatin resistance of NSCLC cells. The sensitivity of platinum promotes cell apoptosis. Conclusion: Matrine can improve the cisplatin resistance of human NSCLC cisplatin-resistant cell line, and the mechanism may be related to the regulation of Nrf2/Annexin A4.
Keywords: non-small cell lung cancer; cisplatin; nuclear factor-E2-related factor; Annexin A4; matrine