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.
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.
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.
Metformin may be an effective chemosensitizer for certain types of CRPC cells, but further investigation is needed.
Anticancer research. 2017 Dec [Epub]
Michelle J Mayer, Laurence H Klotz, Vasundara Venkateswaran
Division of Urology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada., Division of Urology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada .