标题：Carvedilol suppresses malignant proliferation of mammary epithelial cells through inhibition of the ROS-mediated PI3K/AKT signaling pathway
作者：Ma, Zhongbing; Liu, Xingli; Zhang, Qiang; Yu, Zhigang; Gao, Dezong
作者机构：[Ma, Zhongbing; Zhang, Qiang; Yu, Zhigang; Gao, Dezong] Shandong Univ, Hosp 2, 247 Beiyuan St, Jinan 250033, Shandong, Peoples R China.; [Liu, Xingl 更多
通讯作者地址：[Gao, DZ]Shandong Univ, Hosp 2, 247 Beiyuan St, Jinan 250033, Shandong, Peoples R China.
关键词：carvedilol; cancer prevention; reactive oxygen species; phosphoinositide; 3-kinase; protein kinase B signaling pathway
摘要：Reactive oxygen species (ROS) cause oncogenic mutations through direct interaction with DNA. Carvedilol (CAR) exhibits antioxidative activity, and pre-clinical studies have identified that CAR may prevent malignant transformation in certain carcinogenic models. This suggests that CAR may be a potential agent in cancer prevention. In the present study, non-cancerous MCF-10A cells were used as a model to investigate the chemopreventive effect of CAR on benzo(a)pyrene (BaP)-induced cellular carcinogenesis. It was identified that CAR had the ability to eliminate BaP-induced ROS production and subsequent DNA damage. CAR/BaP activated the ROS-mediated phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)(Thr308) signaling pathway, whereas the effectors of the PI3K/AKT signaling pathway, murine double minute 2 (MDM2) and p53(Ser15), served important functions in the BaP/CAR-mediated MCF10A cellular transformation. The results of the present study indicated that CAR may be a novel chemopreventive agent, notably in the prevention of estrogen receptor-negative breast cancer. The antioxidant effects of CAR may contribute to its chemopreventive activity.