Solamargine upregulation of Fas, downregulation of HER2, and enhancement of cytotoxicity using epirubicin in NSCLC cells

doi:10.1002/mnfr.200700044

Chia Nan University of Pharmacy & Science Institutional Repository > 藥理學院 > 化妝品應用與管理系(所) > 期刊論文 > Item 310902800/22184

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標題:	Solamargine upregulation of Fas, downregulation of HER2, and enhancement of cytotoxicity using epirubicin in NSCLC cells
作者:	Chia-Hua Liang Li-Yen Shiu Li-Ching Chang Hamm-Ming Sheu Kou-Wha Kuo
貢獻者:	化粧品應用與管理系
關鍵字:	Epirubicin Fas HER2 NSCLC Solamargine
日期:	2007-07
上傳時間:	2010-01-11 14:08:05 (UTC+8)
摘要:	Nonsmall-cell lung cancer (NSCLC) is not generally a chemosensitive tumor, and the mechanism of resistance to the relevant anticancer drugs has not been fully elucidated. Solamargine (SM), the major steroidal glycoalkaloids extracted from the Chinese herb Solanum, inhibits the growth of human tumor cells. We have previously demonstrated that SM regulates tumor necrosis factor receptors (TNFRs)- and mitochondria-mediated pathways and sensitizes NSCLC cells to initiate apoptosis. Interestingly, this investigation reveals that SM up-regulated Fas expression and down-regulated the expression of HER2, whose overexpression is associated with resistance to drugs, and promotes chemotherapy-induced apoptosis in NSCLC A549 and H441 cells. After treatment with SM, the expression of HER2 mRNA was correlated with the expression of topoisomerase II (TOP2A) mRNA. The combinatory use of low concentrations of SM with low-toxic topoisomerase II inhibitor epirubicin accelerated apoptotic cell death. Therefore, the downregulation of the HER2 and TOP2A expression by SM with epirubicin may partially explain the SM and epirubicin cytotoxicity synergy effect in NSCLC. Results of this study suggest that SM induces Fas and TNFR-induced NSCLC cell apoptosis and reduces HER2 expression. These findings provide the synergistic therapeutic interaction between SM and epirubicin, suggesting that such combinations may be effectively exploited in future human cancer clinical trials.
關聯:	Molecular nutrition and food Research 51(8)： p.999-1005
顯示於類別:	[化妝品應用與管理系(所)] 期刊論文

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