Michelle J Mayer1,2,3, Laurence H Klotz1,2, Vasundara Venkateswaran4,2,3. 1. Division of Urology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. 2. Department of Surgery, University of Toronto, Toronto, ON, Canada. 3. Institute of Medical Science, University of Toronto, Toronto, ON, Canada. 4. Division of Urology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada vasundara.venkateswaran@sunnybrook.ca.
Abstract
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. Copyright
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. Copyright
Authors: Felix B Meyer; Sophie Goebel; Sonja B Spangel; Christiane Leovsky; Doerte Hoelzer; René Thierbach Journal: BMC Cancer Date: 2021-05-28 Impact factor: 4.430