雷公藤红素在体外增强了拉帕替尼对人肝癌细胞的抗癌作用。
Celastrol enhanced the anticancer effect of lapatinib in human hepatocellular carcinoma cells in vitro.
作者信息
Yan Yan-yan, Guo Yan, Zhang Wei, Ma Cun-gen, Zhang Yan-xia, Wang Chen, Wang Hai-xia
机构信息
Medical College, Shanxi Datong University, Datong, Shanxi, People's Republic of China.
出版信息
J BUON. 2014 Apr-Jun;19(2):412-8.
PURPOSE
To investigate whether celastrol could show synergism combined with lapatinib in HepG2 human hepatocellular carcinoma (HCC) cell line in vitro.
METHODS
The effects of treatment with lapatinib and/or celastrol on cell growth were determined using MTT assay. Drug synergy was determined using combination index (CI) methods derived from Chou-Talalay equations using CalcuSyn software. Apoptotic morphology was observed by fluorescence microscope with Hoechst 33258 staining. The expression of EGFR of cell surface was performed by flow cytometry. Changes of apoptotic and growth pathways-related proteins were analysed by Western blotting.
RESULTS
The combination of celastrol and lapatinib produced strong synergy in growth inhibition and apoptosis in vitro in comparison to single-agent treatments. Moreover, celastrol enhanced the ability of lapatinib to down regulate EGFR protein expression in HepG2 cells.
CONCLUSION
These data indicate that the combination of celastrol and lapatinib could be used as a novel combination regimen which could hopefully provide strong anticancer synergy in the treatment of HCC.
目的
研究在体外培养的人肝癌HepG2细胞系中，雷公藤红素与拉帕替尼联合使用是否具有协同作用。
方法
采用MTT法测定拉帕替尼和/或雷公藤红素处理对细胞生长的影响。使用源自Chou-Talalay方程的联合指数（CI）方法，通过CalcuSyn软件测定药物协同作用。用Hoechst 33258染色，通过荧光显微镜观察细胞凋亡形态。采用流式细胞术检测细胞表面表皮生长因子受体（EGFR）的表达。通过蛋白质免疫印迹法分析凋亡和生长相关信号通路蛋白的变化。
结果
与单药治疗相比，雷公藤红素与拉帕替尼联合使用在体外对细胞生长抑制和凋亡具有显著协同作用。此外，雷公藤红素增强了拉帕替尼下调HepG2细胞中EGFR蛋白表达的能力。
结论
这些数据表明，雷公藤红素与拉帕替尼联合使用有望成为一种新型联合治疗方案，为肝癌治疗提供强大的抗癌协同作用。
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