JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2015, Vol. 53 ›› Issue (6): 7-12.doi: 10.6040/j.issn.1671-7554.0.2014.811

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Knockout Grp78 expression increases the sensitivity of hepatoma cells to erlotinib

SONG Jia1, LI Xin2, LI Dan2, YE Liping1   

  1. 1. Department of Pathophysiology, Liaoning Medical University, Jinzhou 121001, Liaoning, China;
    2. Science Laboratory Center, Liaoning Medical University, Jinzhou 121001, Liaoning, China
  • Received:2014-11-11 Revised:2015-03-20 Online:2015-06-10 Published:2015-06-10

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Abstract: Objective To explore the effects of knockout Grp78 expression on the sensitivity of SMMC-7721 cells to erlotinib and the molecular mechanism. Methods The Grp78 expression in SMMC-7721 cells was downregulated with siRNA technique and the expression was identified with Western blotting. The survival rates of cells treated with different concentrations of erlotinib (0, 2.5, 5, 10, 20 μmol/L) were assessed with MTT method. Cell apoptosis was detected with flow cytometry. The morphological changes of apoptosis were evaluated with acridine orange staining. The expression of AKT, p-AKT, ERK and p-ERK were determined with Western blotting. Results The siRNA transfection significantly inhibited Grp78 expression after 24, 48 and 72 hours, and the strongest inhibitive effect appeared after 48 hours (P<0.05). Compared with SMMC-7721/siControl cells, erlotinib significantly inhibited the proliferation and promoted apoptosis of SMMC-7721/siRNA-Grp78 cells (P<0.05), and markedly reduced the expression of p-ERK and p-AKT in SMMC-7721/siRNA-Grp78 cells (P<0.05), while the total protein expression of ERK and AKT were not affected. Conclusion Knockout Grp78 expression increases the sensitivity of hepatoma cells to erlotinib by decreasing the phosphorylation of ERK and AKT.

Key words: Erlotinib, Grp78, Hepatocellular carcinoma

CLC Number: 

  • R735
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