Abstract 1682: Metformin synergistically enhances antitumor efficacy of sorafenib in vitro

Abstract

Abstract Background: Previously, we observed anti-tumor effect of sorafenib in osteosarcoma cells. However, a number of studies suggested that cancer cells might escape from the therapeutic effects of sorafenib though activation of mTOR pathways. Metformin displays significant growth inhibitory effects in several cancer cells by modulating AMPK/Akt/mTOR signaling pathway. We evaluated the effect of metformin in osteosarcoma cells as a single agent, as well as in combination with sorafenib. Methods: The effects of metformin on proliferation, migration and apoptosis of osteosarcoma cells were evaluated using MTT, wound-healing and FACS analysis. To elucidate the mechanisms of cell growth inhibition induced by metformin, we investigated expression of several key signaling proteins in OS cells. The synergistic interactions of metformin and sorafenib were determined by calcusyn analysis. Results: We found that metformin significantly decreased the cell survival, wound-healing capacity of OS cells. Metformin also markedly activated AMPK and decreased the expression of Akt, ERK1/2, mTOR and its downstream target markers. And we observed that addition of sorafenib enhanced antiproliferative and proapoptotic effects of metformin by synergistic modulation of AMPK/Akt/mTOR signaling pathway. Conclusion: We found that metformin exerts therapeutic potentials in OS cells. Currently, studies are underway to evaluate the possibilities of using metformin as an adjuvant therapeutic agent for osteosarcoma, in combination with chemotherapeutic agents or radiotherapy. Citation Format: YUNMI KO, Bo Ra Choi, Jun Ah Lee. Metformin synergistically enhances antitumor efficacy of sorafenib in vitro. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1682. doi:10.1158/1538-7445.AM2014-1682