Presentation Authors: Yi Sun*, Lu Yang, Qiang Wei, Chengdu, China, People's Republic of
Introduction: Both oxidative stress and inflammation play important roles in prostate cancer cell apoptosis or proliferation. However, the mechanisms underlying these processes remain unclear. Thus, we chose IL-8 as the bridge between inflammation and cancer cell oxidative stress-induced death and confirmed its connection with mTOR and GSK-3Î².
Methods: We overexpressed GSK-3Î² and observed the effect of GSK-3Î² on reactive oxygen species (ROS) and cell death induced by oxidative stress. Then, IL-8 was upregulated or downregulated to determine its impact on preventing cells from damage by GSK-3Î²-induced oxidative stress. In addition, we confirmed the role of mTOR in this process through its overexpression or knockdown. Real-time PCR, Western blotting, transcription, Cell Counting Kit 8, flow cytometry and other techniques were used.
Results: IL-8 promotes prostate cancer cell proliferation and decreases apoptosis, while GSK-3Î² induces cell death by oxidative stress through the activation of the caspase-3 signaling pathway by increasing ROS. In addition, mTOR can also decrease the activation of the caspase-3 signaling pathway by inhibiting GSK-3Î² and thus decreasing ROS production. Moreover, the inhibitory effect of IL-8 on GSK-3Î² occurs through the regulation of mTOR.
Conclusions: The results of this study highlight the importance of GSK-3Î², which increases the production of ROS and then induces oxidative stress in tumor cells, while IL-8 and mTOR attenuate the oxidative stress to protect prostate cancer cells through the inhibitor GSK-3Î².
Source of Funding: This study was supported by the National Natural Science Foundation of China (Grant No. 81370855, 81300627 and 81200551), the Prostate Cancer Foundation Young Investigator Award 2013 and Foundation of Science &Technology Department of Sichuan Province (Gr