NVP-BEZ235 induces autophagy of polycystic kidney rat cholangiocytes |
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| Authors: | YE Jing LIU Te-si JIN Xian-guo PIAO Ying-shi ZHAO Yuan-yuan HAN Jing-yi LIN Zhen-hua HARADA Kenichi REN Xiang-shan |
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| Institution: | 1. Department of Pathology, Yanbian University Medical College, Yanbian Hospital of Traditional Chinese Medicine, Yanji 133000, China;
2. Department of Gastroenterology, Yanbian Hospital of Traditional Chinese Medicine, Yanji 133000, China;
3. Department of Pathology, School of Medical Sciences, Kanazawa University, Kanazawa 9208640, Japan |
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| Abstract: | AIM: To explore the effect of dual PI3K/Akt/mTOR inhibitor NVP-BEZ235 on autophagy of polycystic kidney (PCK) rat cholangiocytes. METHODS: The protein levels of p-mTOR and p-Akt in the bile duct epithelial cells were examined by immunohistochemistry. The effect of NVP-BEZ235 on the viability of cholangiocytes was detected by WST-1 assay. The levels of PI3K/Akt/mTOR signaling pathway and autophagy-related proteins with NVP-BEZ235 treatment were determined by Western blot. The effects of LC3 and Beclin 1 silencing, and authophagy-specific inhibitor 3-methyladenine (3-MA) on the cell viability were analyzed by WST-1 assay. RESULTS: The protein levels of p-Akt and p-mTOR were highly increased in the bile duct epithelium of the PCK rats. NVP-BEZ235 significantly inhibited the viability of the cholangiocytes in a dose- and time-dependent manner (P<0.05). NVP-BEZ235 significantly reduced the levels of PI3K/Akt/mTOR signaling pathway-related proteins in the PCK rat cholangiocytes. NVP-BEZ235 upregulated the autophagy-specific proteins LC3 II and Beclin 1. The inhibitory effect of NVP-BEZ235 on the cell viability was weakened by treatment with 3-MA and knockdown of LC3 and Beclin 1 (P<0.01).CONCLUSION: The PI3K/Akt/mTOR inhibitor NVP-BEZ235 suppresses the viability of PCK rat cholangiocytes, and the mechanism is closely related with autophagy. |
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| Keywords: | Autophagy PI3K/Akt/mTOR signaling pathway Polycystic kidney NVP-BEZ235 |
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