IL-8 protects prostate cancer cells from GSK-3ß-induced oxidative stress by activating the mTOR signaling pathway.
Prostate
; 79(10): 1180-1190, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-31104320
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-3ß).METHODS:
We overexpressed GSK-3ß 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-3ß-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-3ß 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-3ß occurs through the regulation of mTOR.CONCLUSION:
The results of this study highlight the importance of GSK-3ß, 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-3ß.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Transdução de Sinais
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Interleucina-8
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Estresse Oxidativo
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Serina-Treonina Quinases TOR
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Glicogênio Sintase Quinase 3 beta
Limite:
Humans
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Male
Idioma:
En
Revista:
Prostate
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China