IL-8 protects prostate cancer cells from GSK-3β-induced oxidative stress by activating the mTOR signaling pathway.

Abstract

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 selected interleukin-8 (IL-8) as the bridge between inflammation and cancer cell oxidative stress-induced death and aimed to confirm its connection with mTOR and Glycogen synthase kinase-3 beta (GSK-3β). We overexpressed GSK-3β and observed its effect on reactive oxygen species (ROS) and oxidative stress-induced cell death. IL-8 was then upregulated or downregulated to determine its impact on preventing cell damage due to GSK-3β-induced oxidative stress. In addition, we overexpressed or knocked down mTOR to confirm its role in this process. Real-time PCR, Western blotting, transcription, Cell Counting Kit 8 (CCK-8), and flow cytometry analyses were performed in addition to the use of other techniques. IL-8 promotes prostate cancer cell proliferation and decreases apoptosis, whereas GSK-3β activates the caspase-3 signaling pathway by increasing ROS and thereby induces oxidative stress-mediated cell death. In addition, mTOR can also decrease activation of the caspase-3 signaling pathway by inhibiting GSK-3 and thus decreasing ROS production. Moreover, the inhibitory effect of IL-8 on GSK-3β occurs through the regulation of mTOR. The results of this study highlight the importance of GSK-3β, which increases the production of ROS and thereby induces oxidative stress in tumor cells, whereas IL-8 and mTOR attenuate oxidative stress to protect prostate cancer cells through inhibition of GSK-3β.