17-AAG协同顺铂抑制肺腺癌A549细胞的增殖

中国临床药理学与治疗学 ›› 2012, Vol. 17 ›› Issue (11): 1240-1244.

17-AAG协同顺铂抑制肺腺癌A549细胞的增殖

王桂平¹, 廖洪映², 韦敏¹, 王妍¹, 周琼¹, 林竹贞¹, 张彦焘¹

¹广州医学院,卫生职业技术学院药学部,广州 510180,广东;
²中山大学附属第三医院心胸外科,广州 510630,广东

收稿日期:2012-05-07 修回日期:2012-09-11 发布日期:2012-12-04
作者简介:王桂平, 男, 博士,主要从事抗肿瘤药物筛选及机制研究。E-mail: docgpwang@yahoo.com.cn
基金资助:
广东省自然科学基金项目(S2011010004147); 广州医学院2011年科研基金博士启动基金(2011C06)

Synergy inhibition effect of 17-AAG in combination with cisplatin on lung adenocarcinoma A549 cells

WANG Gui-ping¹, LIAO Hong-ying², WEI Min¹, WANG Yan¹, ZHOU Qiong¹, LIN Zhu-zhen¹, ZHANG Yan-tao¹

¹Department of Pharmacy, Health College, Guangzhou Medical University, Guangzhou 510180, Guangdond, China;
²Department of Thoracic Surgery, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, Guangdong, China

Received:2012-05-07 Revised:2012-09-11 Published:2012-12-04

摘要/Abstract

摘要： 目的: 观察热休克蛋白90(HSP90)抑制剂17-AAG与顺铂(cisplatin, DDP)联用对肺腺癌细胞株A549增殖抑制的协同效应。方法: 采用四甲基偶氮唑蓝(MTT)法检测不同浓度17-AAG、顺铂及两药联用对肺癌细胞株A549的生长抑制作用,并应用中效原理评价两药联用效应。结果: 顺铂和17-AAG均对A549细胞的生长有较好的抑制作用,并呈现一定的剂量依赖性,顺铂作用 48 h 时,其IC₅₀值为 69.627 μmol/L;17-AAG的IC₅₀值为 0.455 μmol/L。顺铂联合17-AAG显示更强的抑制作用,特别是在低剂量下协同作用更明显。结论: 17-AAG联合顺铂对肺癌细胞的增殖具有协同抑制效应。

关键词: 17-AAG, 顺铂, 肺腺癌, 增殖

Abstract: AIM: The aim of our present study is to assess of synergy inhibition effect of 17-AAG combinated with cisplatin on lung adenocarcinoma A549 cells. METHODS: MTT assay was used to detect the inhibiton of the various concentrations of 17-AAG, cisplatin, or the two combination on A549 cells. The median-effect method of Chou and Talalay was used to evaluate the combination effect. RESULTS: 17-AAG or cisplatin alone inhibited the growth of A549 cells in a concentration-dependent manner. The IC₅₀ for 48 h was 69.627 μmol/L for cisplatin, and 0.455 μmol/L for 17-AAG. The effect was greater when the two agents were combined, even at the lowest dosage combination.CONCLUSION: Our results demonstrated that the combination of 17-AAG and cisplatin showed synergy inhibition effect on lung adenocarcinoma A549 cells.

Key words: 17-AAG, Cisplatin, Lung adenocarcinoma, Cell proliferation

中图分类号:

R965.2

王桂平, 廖洪映, 韦敏, 王妍, 周琼, 林竹贞, 张彦焘. 17-AAG协同顺铂抑制肺腺癌A549细胞的增殖[J]. 中国临床药理学与治疗学, 2012, 17(11): 1240-1244.

WANG Gui-ping, LIAO Hong-ying, WEI Min, WANG Yan, ZHOU Qiong, LIN Zhu-zhen, ZHANG Yan-tao. Synergy inhibition effect of 17-AAG in combination with cisplatin on lung adenocarcinoma A549 cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(11): 1240-1244.

参考文献

[1] Overman MJ, Kazmi SM, Jhamb J, et al.Weekly docetaxel, cisplatin, and 5-fluorouracil as initial therapy for patients with advanced gastric and esophageal cancer[J]. Cancer, 2010,116(6): 1446-1453.
[2] Shen FZ, Wang J, Liang J, et al.Low-dose metronomic chemotherapy with cisplatin: can it suppress angiogenesis in H22 hepatocarcinoma cells[J]. Int J Exp Pathol, 2010, 91(1): 10-16.
[3] Silver DP, Richardson AL, Eklund AC, et al.Efficacy of neoadjuvant cisplatin in triple-negative breast cancer[J]. J Clin Oncol, 2010, 28(7): 1145-1153.
[4] 王艇, 马彬, 杨克虎, 等. 第三代药物为基础的三药方案对比两药方案化学治疗晚期非小细胞肺癌的系统评价[J]. 中国肺癌杂志, 2009, 12(6): 565-570.
[5] Neckers L, Ivy SP.Heat shock protein 90[J]. Current Opinion in Oncology, 2003, 15(6): 419-424.
[6] Young JC, Moarefi I, Hartl FU.HSP90: a specialized but essential protein-folding tool[J]. J Cell Biol, 2001, 154(2): 267-274.
[7] Pacey S, Banerji U, Judson I, et al.HSP90 inhibitors in the clinic[J]. Handb Exp Pharmacol, 2006; (172): 331-358.
[8] Watanabe G, Behrns K, Kim J, et al.Heat shock protein 90 inhibition abrogates hepatocellular cancer growth through cdc2-mediated G2/M cell cycle arrest and apoptosis[J]. Cancer Chemother Pharmacol, 2009, 64(3): 433-443.
[9] Solit DB, Zheng FF, Drobnjak M, et al.17-Allylamino-17-demethoxygeldanamycin induces the degradation of androgen receptor and HER-2/neu and inhibits the growth of prostate cancer xenografts[J]. Clin Cancer Res, 2002, 8(5): 986-993.
[10] Haithcock BE, Stinchcombe TE, Socinski MA.Treatment of surgically resectable non-small-cell lung cancer in elderly patients.[J]. Clin Lung Cancer, 2009, 10(6): 405-409.
[11] Ueda Y, Igishi T, Hashimoto K, et al.Synergistic cell growth inhibition by the combination of amrubicin and Akt-suppressing tyrosine kinase inhibitors in small cell lung cancer cells: implication of c-Src and its inhibitor[J]. Int J Oncol, 2009, 34(3): 689-696.
[12] Xu SP, Sun GP, Shen YX, et al.Synergistic effect of combining paeonol and cisplatin on apoptotic induction of human hepatoma cell lines[J]. Acta Pharmacol Sin, 2007, 28(6): 869-878.
[13] Wan XA, Sun GP, Wang H, et al.Synergistic effect of paeonol and cisplatin on oesophageal cancer cell lines[J]. Dig Liver Dis, 2008, 40(7): 531-539.
[14] Goetz MP, Toft DO, Ames MM, et al.The HSP90 chaperone complex as a novel target for cancer therapy[J]. Ann Oncol, 2003, 14(8): 1169-1176.
[15] Bagatell R, Beliakoff J, David CL, et al.HSP90 inhibitors deplete key anti-apoptotic proteins in pediatric solid tumor cells and demonstrate synergistic anticancer activity with cisplatin[J]. Int J Cancer, 2005, 113(2): 179-188.
[16] Gennings C.An efficient experimental design for detecting departure from additivity in mixtures of many chemicals[J]. Toxicology, 1995, 105(2/3): 189-197.
[17] 蔡芸, 裴斐, 郑砚君, 等. 大蒜素联合头孢唑林或苯唑西林对葡萄球菌的抗菌作用[J]. 中国临床药理学与治疗学, 2006, 11(8): 925-928.
[18] Jung JY, Song SH, Kim TY, et al.The Synergism between Belotecan and Cisplatin in Gastric Cancer[J]. Cancer Res Treat, 2006, 38(3): 159-167.
[19] 陈姝, 汤为学, 娄世锋. 中效原理在体外抗癌药物定量分析中的应用[J]. 肿瘤防治研究, 2004, 31(5): 270-272.