Journal of Jilin University Medicine Edition ›› 2015, Vol. 41 ›› Issue (03): 470-475.doi: 10.13481/j.1671-587x.20150307

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Induction of As2O3 in combination with γ-secretase inhibitor on apoptosis of HepG2 and its mechanism

ZHOU Ming1,2, WANG Xuewen1,2, YANG Li1,2, SONG Hailin1,2, DUAN Jingjing1,2   

  1. 1. School of Medical Science, Shihezi University, Key laboratory for Xinjiang Endemic Diseases and Ethnic Diseases with High Incidence, Ministry of Education, Shihezi 832002, China;
    2. Department of Pathophysiology, School of Medical Science, Shihezi University, Shihezi 832002, China
  • Received:2014-09-20 Published:2015-08-01

Abstract:

Objective To discuss the effect of As2O3 on the apoptosis of HepG2 cells via Notch signal pathway, and to clarify its mechanism. Methods The HepG2 cells cultured in vitro were divided into blank group, As2O3 group, MW167 group and combination group.The HepG2 cells were treated with As2O3 and MW167 at different concentrations for 24, 48 and 72 h, and the inhibitory rates of proliferations of the HepG2 cells were detected by MTT method.The HepG2 cells in various groups were intervened by MW167 and As2O3 at non-cytotoxic doses (As2O3 0.25 mg·L-1, MW167 10 μmol·L-1) based on The Results of MTT for 48 h, then the apoptotic rate was tested by flow cytometry;RT-PCR and Western blotting Methods were employed to detect the expressions of Notch-1, Bcl-2 and Caspase-3 mRNA and protein. Results The HepG2 cells treated with both As2O3 and MW167 at different concentrations could inhibit the cell proliferation and showed a dose-effect relationship.For the HepG2 cells in different groups treated with MW167 group and As2O3 group at non-cytotoxic doses for 48 h, compared with blank group, the apoptotic rates in As2O3 group, MW167 group and combination group were increased(P<0.05), especially in combination group; the expression levels of Bcl-2, Notch-1 mRNA and protein in As2O3 group, MW167 group and combination group were lower than those in blank group(P<0.05), especially in combination group;compared with blank group, the expressions levels of Caspase-3 mRNA and protein in As2O3 group, MW167 group and combination group were increased(P<0.05), especially in combination group. Conclusion As2O3 can induce the apoptosis of hepatocelular carcinoma HepG2 cells and the mechanism may be related to the down-regulation of Bcl-2 and Notch-1 and up-regulation of Caspase-3 mRNA and protein through Notch signal pathway.

Key words: HepG2 cells, γ-secretase inhibitor, arsenic trioxide, apoptosis

CLC Number: 

  • R735.7