Abstract 1301: Metformin induces cytotoxicity by TP and ERCC1 decrease.

Abstract

Abstract Metformin is an anti-diabetic drug recently shown to inhibit cancer cell proliferation and growth, although the involved molecular mechanisms have not been elucidated. In many cancer cells, highly expression of thymidine phosphorylase (TP) and ERCC1 are associated with poor prognosis. We used A549 and H1975 huamn non-small cell lung cancer (NSCLC) cell lines to investigate the role of TP and ERCC1 expression in metformin-induced cytotoxicity. Metformin treatment decreased cellular TP and ERCC1 protein and mRNA levels by down-regulating phosphorylated MEK1/2-ERK1/2 protein levels in a dose- and time-dependent manner. The enforced expression of the constitutively active MEK1 (MEK1-CA) vectors significantly restored cellular TP and ERCC1 protein levels and cells viability. Specific inhibition of TP and ERCC1 expression by siRNA enhanced the metformin-induced cytotoxicity and growth inhibition. In conclusion, metformin induces cytotoxicity by down-regulating TP and ERCC1 expression in NSCLC cells. Citation Format: Yun-Wei Lin, Yu-Ching Huang, Sheng-Chieh Tseng, Hsien-Chun Chiu, Huang-Jen Chen, Yi-Jhen Huang, Ting-Yu Wo, Shao-Hsing Weng, Jen-Chung Ko. Metformin induces cytotoxicity by TP and ERCC1 decrease. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1301. doi:10.1158/1538-7445.AM2013-1301