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, 410013, Hunan, P. R. China.
Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, P. R. China.
Cancer Commun (Lond). 2018 Jul 27;38(1):50. doi: 10.1186/s40880-018-0319-7.
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.
在之前的研究中，我们已经表明二甲双胍和吉非替尼的联合抑制了膀胱癌细胞的生长。在这里，我们研究了二甲双胍类似物苯乙双胍，无论是单独使用还是与吉非替尼联合使用，是否可以抑制膀胱癌细胞的生长。
采用 MTT 和集落形成实验检测苯乙双胍和吉非替尼对一种鼠和两种人膀胱癌细胞系生长的抑制作用。在划痕愈合实验中评估对细胞迁移的影响。使用 CompuSyn 软件评估两种药物之间的协同作用。使用 Western blot 探索苯乙双胍和吉非替尼作用中 AMPK 和 EGFR 途径的潜在参与。
在 MTT 和集落形成实验中，苯乙双胍在抑制膀胱癌细胞生长方面比二甲双胍强 10 多倍。苯乙双胍在划痕愈合实验中也能强烈抑制细胞迁移，并促进细胞凋亡。激活 AMPK 信号通路；抑制 EGFR 信号通路。苯乙双胍与吉非替尼具有协同作用，药物联合使用比单独使用苯乙双胍具有更强的抗癌活性和凋亡激活作用。
苯乙双胍具有作为单独或与吉非替尼联合治疗膀胱癌的有效药物的潜力。
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