Mechanism of PI3K/AKT/mTOR signaling pathway on apoptosis of hepatocyte induced by GCDC

doi:10.12092/j.issn.1009-2501.2019.02.001

Abstract

Abstract:

AIM: To investigate the effects of PI3K/AKT/mTOR signaling pathway on proliferation and apoptosis of human hepatocyte HL-7702 induced by GCDC. METHODS: HL-7702 cells were divided into control group, GCDC group (1 mmol/L GCDC pretreated cells for 4 hours), GCDC+LY294002 group (GCDC treated cells for 4 hours, LY294002 treated cells for 24 hours) and GCDC+IGF-1 group (GCDC treated cells for 4 hours, 20 nmol/L of IGF-1 treated cells for 24 hours). After treatment, the expressions of PI3K, AKT, p-AKT, mTOR, p-mTOR, Bcl-2, Bax and Nrf2 were detected by Western blot; the proliferation and apoptotic rates were detected by MTT and Annexin V-FITC/PI double staining,respectively.The content of ROS was detected by fluorescent DCFH-DA probe. RESULTS: GCDC could significantly down-regulate the expression of PI3K, p-AKT, p-mTOR, Bcl-2 and Nrf2 in HL-7702 cells, up-regulate the expression of Bax, inhibit cell proliferation, induce apoptosis and induce ROS production (P<0.05). LY294002 could enhance the effect of GCDC on proliferation, apoptosis, ROS level and PI3K, p-AKT, p-mTOR, Bcl-2, Bax and Nrf2 expression of HL-7702 cells; IGF-1 vice versa. CONCLUSION: Activation of PI3K/AKT/mTOR signaling pathway can improve bile liver fibrosis, and the mechanism may be related to anti-apoptosis and anti-oxidation.

Key words: PI3K/AKT/mTOR signaling pathway, glycochenodeoxycholate, hepatocyte injury, oxidative stress

CLC Number:

R965.2

WENG Dandan, WANG Junbo, LI Guangxiao. Mechanism of PI3K/AKT/mTOR signaling pathway on apoptosis of hepatocyte induced by GCDC[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(2): 121-127.

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