邻硝基苯基靛红查尔酮单用或与抗癌药或抑制剂联用的抗癌活性

基础医学与临床 ›› 2013, Vol. 33 ›› Issue (12): 1544-1548.

邻硝基苯基靛红查尔酮单用或与抗癌药或抑制剂联用的抗癌活性

戚雨婷¹,张丽君²,赵翔³,张页⁴

1. 北京大学医学部基础医学院
2. 北京大学生命科学学院
3. 北京大学基础医学院细胞生物系
4. 北京大学基础医学院

收稿日期:2013-07-05 修回日期:2013-09-23 出版日期:2013-12-05 发布日期:2013-11-28
通讯作者: 张页 E-mail:zhangye@bjmu.edu.cn
基金资助:
国家自然科学基金(地区基金)

The anticancer activities of an isatin chalcone used alone or in combinations with anticancer drugs or inhibitors

Received:2013-07-05 Revised:2013-09-23 Online:2013-12-05 Published:2013-11-28

摘要/Abstract

摘要： 目的研究邻硝基苯基靛红查尔酮（ONIC）单独和联合用药的抗癌效果并分析其机制。方法检测ONIC对体外培养癌细胞的增殖抑制。用Chou氏法和金氏法探讨ONIC与10种抗癌药或通路抑制剂的联用效果。结果 ONIC对8种癌细胞系均有显著抗癌活性。与ONIC有协同作用的药物有5种：HSP90抑制剂17-AAG、Arf抑制剂布雷菲德菌素A、蛋白酶体抑制剂硼替佐米、mTOR抑制剂雷帕霉素、ERK1/2抑制剂U0126。与ONIC拮抗的药物有3种：RhoA抑制剂法舒地尔、PI3K抑制剂LY294002、LKB1-AMPK激动剂甲福明。微管稳定剂紫杉醇和Rac1抑制剂NSC23766与ONIC有叠加作用。结论 ONIC不仅自身有强抗癌活性，而且与不同药物联用具有特异的协同或拮抗效果，提示其机制可能与ONIC作用于RhoA和mTOR的上下游通路有关。

关键词: 关键词：靛红, 查尔酮, 抗癌药, 协同作用, 联合用药

Abstract: Objective Investigate anticancer effects and mechanisms of o-nitrobenzyl-isatinyl chalcone (ONIC) used alone or in drug combination. Method Detection of proliferation inhibition on cultured cancer cells treated with ONIC. Using Chou’s and Jin’s methods to evaluate drug combination effects among ONIC and ten anticancer drugs or pathway inhibitors. Result ONIC had potent in vitro anticancer activity against eight cancer cell lines. Five drugs were shown to have synergetic effects with ONIC: HSP 90 inhibitor 17-AAG, Arf inhibitor brefeldin A, proteasome inhibitor bortezomib, mTOR inhibitor rapamycin, and ERK1/2 inhibitor U0126. Antagonistic effects were revealed among ONIC and three drugs: RhoA inhibitor fasudil, PI3K inhibitor LY294002, and LKB1-AMPK agonist metformin. Both the microtubule stabilizer paclitaxel and Rac1 inhibitor NSC23766 showed additive effects with ONIC. Conclusion ONIC not only itself has potent anticancer activity, but also has specific synergetic or antagonistic effects in combination with other drugs, suggesting that the RhoA pathway and the up- and downstream elements in mTOR pathway were closely related with the anticancer mechanisms of ONIC.

Key words: Key words: isatin, chalcone, anticancer drugs, synergy, drug combination

中图分类号:

Q 279

戚雨婷张丽君赵翔张页. 邻硝基苯基靛红查尔酮单用或与抗癌药或抑制剂联用的抗癌活性[J]. 基础医学与临床, 2013, 33(12): 1544-1548.

[1]	王俊张逸曹明月黄薇杨楠刘雁勇. HSP90靶向抑制剂P7与阿霉素联用对急性髓性白血病细胞凋亡的协同增效作用[J]. 基础医学与临床, 2019, 39(6): 821-825.
[2]	范姝婕刘俊雅王俊刘娜斯黄薇杨楠刘雁勇. HSP90靶向抑制剂P7与多西紫杉醇联用在三阴性乳腺癌细胞的协同抗肿瘤作用[J]. 基础医学与临床, 2018, 38(5): 659-663.
[3]	纪春梅甄永占范晓禹王志军蒋守芳朱丽华章广玲. 赖氨大黄酸与顺铂联合对人肺癌A549细胞株增殖和凋亡的影响[J]. 基础医学与临床, 2014, 34(2): 155-159.
[4]	周佳彦段金虹孙昭胡燕朱广瑾杨先达. 白藜芦醇与表阿霉素联合用药对多种人类肿瘤细胞的体外抑制作用[J]. 基础医学与临床, 2010, 30(11): 1149-1152.
[5]	张高峰李刚许永光. 丙泊酚联合不同剂量咪达唑仑在长时间显微外科手术患者中的镇静[J]. 基础医学与临床, 2008, 28(7): 774-777.