91桃色

Abstract

Epigallocatechin-3-gallate (EGCG) is a major polyphenol component in green tea and is widely studied as a cancer chemopreventive agent with potential anticancer effect. The major mechanism of EGCG-mediated anticancer effects is induction of apoptosis. However, it has been shown that different tumor cells have different sensitivity upon treatment of EGCG and Nrf2/HO-1 signaling pathway contributes to resistance to apoptosis induced by EGCG. Metformin is the first-line drug of choice for the treatment of type 2 diabetes worldwide. We hypothesize that metformin may influence the efficacy of EGCG to lung cancer cells. We found that metformin sensitizes lung cancer A549 and H460 to EGCG, by inducing apoptosis and elevating ROS level, while showed much less impact on normal lung epithelial BEAS-2B cells. Metformin plus EGCG inhibited tumor growth in vivo. We also found that metformin could not only decrease the protein level of Nrf2 but also inhibit Nrf2 nuclear translocation induced by EGCG, thus inhibiting the protein level of HO-1. Moreover, the acetylation of Nrf2 is regulated by EGCG and metformin, which may explain the change of Nrf2 translocation. Furthermore, metformin augments the anti-proliferation effect of other green tea extracts in A549 cells. Therefore, EGCG plus metformin might be a more efficient way to chemo-prevent lung cancer than EGCG alone.

Biography

Email: jpcao@suda.edu.cn