丁烷硒啉和顺铂联合给药对肿瘤细胞的协同效应分析

doi:10.5246/jcps.2017.08.067

中国药学(英文版) ›› 2017, Vol. 26 ›› Issue (8): 595-604.DOI: 10.5246/jcps.2017.08.067

丁烷硒啉和顺铂联合给药对肿瘤细胞的协同效应分析

邹乔^1,2, 陈伊凡^1,2, 郑小青^1,2, 徐彬瑗^1,2, 刘禹锡^1,2, 曾慧慧^1,2*

1. 北京大学医学部药学院天然药物及仿生药物国家重点实验室, 北京 100191
2. 北京大学医学部药学院化学生物学系, 北京 100191

收稿日期:2017-05-12 修回日期:2017-06-23 出版日期:2017-08-31 发布日期:2017-07-15
通讯作者: Tel.: +86-010-62015584, E-mail: zenghh@bjmu.edu.cn
基金资助:
The National Natural Science Foundation (Grant No. 81372266) and National Science and Technology Major Project, People’s Republic of China (Grant No. 2011zx09101-001-03).

Butaselen and cisplatin synergistically inhibit human cancer cells proliferation

Qiao Zou^1,2, Yifan Chen^1,2, Xiaoqing Zheng^1,2, Binyuan Xu^1,2, Yuxi Liu^1,2, Huihui Zeng^1,2*

1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2017-05-12 Revised:2017-06-23 Online:2017-08-31 Published:2017-07-15
Contact: Tel.: +86-010-62015584, E-mail: zenghh@bjmu.edu.cn
Supported by:
The National Natural Science Foundation (Grant No. 81372266) and National Science and Technology Major Project, People’s Republic of China (Grant No. 2011zx09101-001-03).

摘要/Abstract

摘要：

顺铂是一种含铂药物, 目前已被广泛应用于多种癌症的治疗。然而, 顺铂的副作用限制了其在临床的应用。丁烷硒啉(BS)是我们实验室自主设计的TrxR抑制剂, 在体内和体外均显示出抗肿瘤作用。在本研究中, 我们考察了丁烷硒啉和顺铂在BEL-7402细胞, LoVo细胞, HeLa细胞和A549细胞中的联合作用。丁烷硒啉和顺铂联合给药时具有协同作用,尤其是BEL-7402细胞。细胞凋亡分析显示, 在BEL-7402细胞中, 丁烷硒啉和顺铂联合(1:1)给药48小时能够诱导更高的凋亡效应。在BEL-7402细胞中的进一步研究表明, 协同作用可能是Bcl-2/Bax蛋白表达比例急剧下降所致。总之, 顺铂与丁烷硒啉联用可能是化疗治疗中有应用前景的策略之一。

关键词: 丁烷硒啉, 顺铂, 协同作用, Bcl-2, Bax

Abstract:

Cisplatin (CDDP), a platinum-containing drug, has been widely used in the therapy of many types of cancers today. However, the side effects of CDDP have limited its clinical application. Butaselen (BS), a TrxR inhibitor designed by our group, has shown anti-tumor effects in vivo and in vitro. In this study, we investigated the combinatory effects of BS and CDDP on BEL-7402 cells, LoVo cells, HeLa cells and A549 cells. We observed synergistic effects when BS and CDDP were used in combination, especially in BEL-7402 cells. Apoptosis analysis also revealed that the combination treatment of BS and CDDP (1:1) for 48 h induced higher apoptotic effects in BEL-7402 cells. A further study in BEL-7402 cells showed that the synergistic effect might be mediated by the sharp reduction of ratio of Bcl-2/Bax protein. Taken together, the combination of CDDP and BS might be of great potential for chemotherapy.

Key words: Butaselen, Cisplatin, Synergistic effect, Bcl-2, Bax

中图分类号:

R916.4

Supporting:

邹乔, 陈伊凡, 郑小青, 徐彬瑗, 刘禹锡, 曾慧慧. 丁烷硒啉和顺铂联合给药对肿瘤细胞的协同效应分析[J]. 中国药学(英文版), 2017, 26(8): 595-604.

Qiao Zou, Yifan Chen, Xiaoqing Zheng, Binyuan Xu, Yuxi Liu, Huihui Zeng. Butaselen and cisplatin synergistically inhibit human cancer cells proliferation[J]. Journal of Chinese Pharmaceutical Sciences, 2017, 26(8): 595-604.

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丁烷硒啉和顺铂联合给药对肿瘤细胞的协同效应分析

Butaselen and cisplatin synergistically inhibit human cancer cells proliferation

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