Phenformin alone or combined with gefitinib inhibits bladder cancer via AMPK and EGFR pathways

Cancer Communications

Xiaoping Yang¹  Ting Tao²  Kwame Oteng Darko²  Sichun Zhou²  Yanjun Huang²  Qiongli Su²  Mei Peng²  Caimei He²  Jun Deng² 

[1] Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, P. R. China;Key Laboratory of Study and Discovery of Targeted Small Molecules of Hunan Province and Department of Pharmacy in the School of Medicine and Laboratory of Animal Nutrition and Human Health, Hunan Normal University, Changsha, P. R. China

关键词: Phenformin;    Gefitinib;    Bladder cancer;    AMPK;    EGFR;   

DOI  :  10.1186/s40880-018-0319-7

学科分类：肿瘤学

来源: Springer

【 摘 要 】

In previous studies, we have shown that the combination of metformin and gefitinib inhibits the growth of bladder cancer cells. Here we examined whether the metformin analogue phenformin, either used alone or in combination with gefitinib, could inhibit growth of bladder cancer cells. The growth-inhibitory effects of phenformin and gefitinib were tested in one murine and two human bladder cancer cell lines using MTT and clonogenic assays. Effects on cell migration were assessed in a wound healing assay. Synergistic action between the two drugs was assessed using CompuSyn software. The potential involvement of AMPK and EGFR pathways in the effects of phenformin and gefitinib was explored using Western blotting. In MTT and clonogenic assays, phenformin was > 10-fold more potent than metformin in inhibiting bladder cancer cell growth. Phenformin also potently inhibited cell migration in wound healing assays, and promoted apoptosis. AMPK signaling was activated; EGFR signaling was inhibited. Phenformin was synergistic with gefitinib, with the combination of drugs showing much stronger anticancer activity and apoptotic activation than phenformin alone. Phenformin shows potential as an effective drug against bladder cancer, either alone or in combination with gefitinib.

【 授权许可】

CC BY