评估二甲双胍在去势抵抗性前列腺癌细胞中与多西他赛化疗联合使用时作为潜在化学增敏剂的作用。
Evaluating Metformin as a Potential Chemosensitizing Agent when Combined with Docetaxel Chemotherapy in Castration-resistant Prostate Cancer Cells.
作者信息
Mayer Michelle J, Klotz Laurence H, Venkateswaran Vasundara
机构信息
Division of Urology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Department of Surgery, University of Toronto, Toronto, ON, Canada.
出版信息
Anticancer Res. 2017 Dec;37(12):6601-6607. doi: 10.21873/anticanres.12117.
BACKGROUND/AIM: Docetaxel, the first-line chemotherapy for metastatic castration-resistant prostate cancer (mCRPC), provides certain survival benefits, but is associated with significant toxicity. A novel therapeutic approach for mCRPC is combining docetaxel with a chemosensitizing agent. We hypothesized that metformin, a potential chemosensitizer, would improve docetaxel efficacy in CRPC cells.
MATERIALS AND METHODS
MTS assays were used to determine the effect of metformin-docetaxel treatment on PC3 and DU145 cell viability. Wound-healing and ATP concentration assays were used to evaluate cell migration and intracellular ATP levels following metformin-docetaxel treatment. Western blotting was used for mechanistic evaluation.
RESULTS
Metformin-docetaxel treatment significantly reduced PC3 cell viability. Metformin-docetaxel treatment did not significantly affect cell migration or intracellular ATP levels. Western blotting revealed metformin-docetaxel treatment did not significantly change AMPK or P-AMPK expression patterns.
CONCLUSION
Metformin may be an effective chemosensitizer for certain types of CRPC cells, but further investigation is needed.
背景/目的：多西他赛是转移性去势抵抗性前列腺癌（mCRPC）的一线化疗药物，可提供一定的生存益处，但具有显著毒性。mCRPC的一种新型治疗方法是将多西他赛与化学增敏剂联合使用。我们假设，作为一种潜在化学增敏剂的二甲双胍可提高多西他赛对CRPC细胞的疗效。
材料与方法
采用MTS试验确定二甲双胍-多西他赛治疗对PC3和DU145细胞活力的影响。采用伤口愈合试验和ATP浓度测定评估二甲双胍-多西他赛治疗后的细胞迁移和细胞内ATP水平。采用蛋白质印迹法进行机制评估。
结果
二甲双胍-多西他赛治疗显著降低了PC3细胞活力。二甲双胍-多西他赛治疗对细胞迁移或细胞内ATP水平无显著影响。蛋白质印迹显示，二甲双胍-多西他赛治疗未显著改变AMPK或P-AMPK表达模式。
结论
二甲双胍可能是某些类型CRPC细胞的有效化学增敏剂，但仍需进一步研究。
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