The water-soluble tetrazolium salt (WST) cell viability assay and colony formation assays was performed to investigate the effects of metformin, everolimus and their combination on normal kidney epithelial cells (HK-2, LLC-PK1) and RCC (Cakil, Caki2) cell growth. Signaling molecules involved in mTOR signaling was analyzed by immunoblot analysis of various proteins including mTOR, AMPK, 4EBP1, p70S6K.
WST cell viability assay showed that both metformin and everolimus reduced cell viability of normal kidney cells and renal cancer cells in a dose-dependent manner. Metformin combined with everolimus had a synergistic inhibitory effect in a dose-dependent manner. In Caki-2 cell, metformin combined with everolimus effectively inhibited colony formation. Additionally, this combination inhibited mTOR down signaling molecules, AMPK, 4EBP1, p70S6K in Caki-2 cell.
This study demonstrates the synergic antitumor effects between metformin and everolimus, which could potentially be a prospective therapeutic strategy to achieve potent antitumor effects on renal cell carcinoma.
Presented by: Young Eun Yoon, South Korea
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre. Twitter: @GoldbergHanan at the 37th Congress of Société Internationale d’Urologie - October 19-22, 2017- Lisbon, Portugal