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

Abstract

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 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). Methods 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. Results 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. Conclusion 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.

N-cadherin inhibitor creates a microenvironment that protect TILs from immune checkpoints and Treg cells

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“…58 IL-8 inhibition was achieved as previously described. 43 Briefly, cells were transfected with 100 nM DNA single clone plasmids containing a shRNA to silence IL-8 (category number C01001; GenePharma, Shanghai, China) using the transfection reagent Lipofectamine 3000 (Invitrogen, Carlsbad, California, USA) according to the manufacturer's instructions.…”

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Interleukin-8 in Melanoma Pathogenesis, Prognosis and Therapy—An Integrated View into Other Neoplasms and Chemokine Networks

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