去甲氧基薑黃素通過降解 HER2 和抑制 PI3K/Akt 路徑誘導 HER2 過表達膀胱癌細胞凋亡

施孟宏^1,2、高建璋²、楊明昕²、查岱龍²、孫光煥²、吳勝堂²、魏宗德³

國軍高雄總醫院左營分院外科部¹;國防醫學院三軍總醫院外科部泌尿外科²;中國醫藥大學生命科學院生物科技學系³

Demethoxycurcumin Induces Apoptosis in HER2 Overexpressing Bladder Cancer Cells through Degradation of HER2 and Inhibiting the PI3K/Akt Pathway

Menghung Shih^1,2、Chien-Chang Kao²、Ming-Hsin Yang²、Tai-Lung Cha²、Guang-Huan Sun²、Sheng-Tang Wu²、Tzong-Der Way³

Department of Surgery, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan¹;Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan²; Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan³

Purpose: The aim of this study is to evaluate whether curcuminoids (curcumin, demethoxycurcumin(DMC), and bisdemethoxycurcumin) could repress the expression of HER2 in HER2-overexpressing bladder cancer cells

Materials and Methods :

The human bladder cancer cell lines RT4 (overexpress HER2), and TCCSUP (express the basal level of HER2) were obtained from ATCC (Rockville, MD, USA). In addition, TCCSUP/HER2 was stably transfected with pSV2-HER2. RPMI 1640 was used for the maintenance of TCCSUP cells and Dulbecco‘s modified eagle medium was used for RT4 cells and supplemented with 10% fetal bovine serum. Cells were grown in a humidified incubator at 37C under 5% CO2 in air.

Result: Among the test compounds, DMC significantly suppressed the expression of HER2, and preferentially inhibited cell proliferation and induced apoptosis in HER2-overexpressing bladder cancer cells. DMC decreases HER2 level through inhibiting the interaction of HER2 and Hsp90. Our study also indicated that DMC showed additive activity in combination with chemotherapeutic agents, including paclitaxel and cisplatin.

Conclusion:

These findings show that DMC should be developed further as a new antitumor drug candidate for treatment of HER2-overexpressing bladder cancer.