Effects of Pin1 on Proliferation and Apoptosis of HepG2 Cells Under Endoplasmic Reticulum Stress

Objective To investigate the expression of Pin1 protein in HepG2 cells under endoplasmic reticulum stress (ERS) and its effect on cell proliferation and apoptosis.

Methods The THLE3 cells were treated with tunicamycin (TM) (TM group) or DMSO (DMSO group) for 48h. The HepG2 cells were treated with TM (TM group), ATRA(ATRA group), TM+ATRA (TM+ATRA group) or DMSO (DMSO group) for 48h. The protein levels of Bip and Pin1 were detected by Western blot, cell proliferation was detected by CCK-8 assay, and cell apoptosis was detected by flow cytometry.

Results The expression of Bip both increased in THLE3 and HepG2 cells treated with TM, indicated that TM effectively induced ERS in cells. Compared with the DMSO group, the protein level of Pin1 in THLE3 cells in TM group was decreased with the increasing of TM concentration (P < 0.001). In TM+ATRA group, with the increasing of TM concentration, the expression of Pin1 was decreased in HepG2 cells (P < 0.01). The inhibitory rates was (29.33±4.73)% in HepG2 cells in TM group, significantly lower than (60.33±2.08)% in THLE3 cells in TM group (P < 0.001). In TM+ATRA group, the growth inhibition rates was increased to (60.33±6.03)% in HepG2 cells. The apoptosis rate of THLE3 cells in TM group was (22.25±0.78)%, significantly higher than (3.57±0.31)% in DMSO group (P < 0.01). The apoptosis rates of HepG2 cells in ATRA group and TM+ATRA group were significantly higher than that in the DMSO group ((10.03±0.49)% vs. (5.10±1.00)%, P < 0.05 and (23.70±0.75)% vs. (5.10±1.00)%, P < 0.01).

Conclusions HepG2 cells resist ERS-induced apoptosis by maintaining Pin1 protein level. Reducing the protein level of Pin1 can significantly inhibit the cell proliferation and induce apoptosis.