Yan Yan-Yan, Bi Hong, Zhang Wei, Wen Qing, Liu Hong, Li Jin-Xia, Zhang Hui-Zhi, Zhang Yan-Xia, Li Jia-Shan
Institute of Respiratory and Occupational Diseases; Collaborative Innovation Center for Cancer; Medical College, Shanxi Datong University, Datong, Shanxi, China.
J BUON. 2017 May-Jun;22(3):644-651.
To investigate the effect and related molecular mechanisms of lapatinib/celastrol combination or single-agent treatment in HER2/neu-overexpressing MDA-MB-453 breast cancer cells.
The effects of treatment with lapatinib, celastrol or their combination on cell growth were determined using MTT assay. Drug synergy was determined using the combination index (CI) methods derived from Chou-Talalay equations using CalcuSyn software. Apoptotic morphology was observed by fluorescence microscope with Hoechst 33258 staining. Changes of apoptotic and growth pathways-related proteins were analysed by Western blot. The expression of HER2 of cell surface was performed by flow cytometry. Subcellular distribution of HER2 was observed by immunofluorescence study.
Combination celastrol and lapatinib produced strong synergy in growth inhibition and apoptosis in comparison to single-agent treatment in HER2/neu-overexpressing MDA-MB-453 cells. Interestingly, compared with celastrol treatment alone, lapatinib/celastrol combination induced more HER2 membrane protein downregulation and ectopic to cytoplasm and nucleus in MDA-MB-453 cells.
The combination of celastrol and lapatinib could be used as a novel combination regimen which provides a strong anticancer synergy in the treatment of HER2/neu-overexpressing cancer cells.
研究拉帕替尼/雷公藤红素联合或单药治疗对HER2/neu过表达的MDA-MB-453乳腺癌细胞的作用及相关分子机制。
采用MTT法测定拉帕替尼、雷公藤红素或其联合用药对细胞生长的影响。使用源自Chou-Talalay方程的联合指数（CI）方法，通过CalcuSyn软件确定药物协同作用。用Hoechst 33258染色，通过荧光显微镜观察凋亡形态。通过蛋白质印迹法分析凋亡和生长途径相关蛋白的变化。通过流式细胞术检测细胞表面HER2的表达。通过免疫荧光研究观察HER2的亚细胞分布。
与单药治疗相比，雷公藤红素和拉帕替尼联合用药在HER2/neu过表达的MDA-MB-453细胞的生长抑制和凋亡方面产生了强烈的协同作用。有趣的是，与单独使用雷公藤红素治疗相比，拉帕替尼/雷公藤红素联合用药在MDA-MB-453细胞中诱导更多HER2膜蛋白下调并异位至细胞质和细胞核。
雷公藤红素和拉帕替尼联合用药可作为一种新型联合治疗方案，在治疗HER2/neu过表达的癌细胞方面具有强大的抗癌协同作用。
