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    Zhonghua Zhong Liu Za Zhi. 2008 Jul;30(7):494-7.

    [Impact of PI3K /Akt /mdm2 signaling pathway on the sensitivity of gastric cancer cell line SGC7901 to doxorubicin].

    [Article in Chinese]
    Ai YW, Yu HG, Yu JP, Yang Y, Li H, Hu XW, Luo HS.

    Source

    Department of Gastroenterology, People's Hospital of Wuhan University, Wuhan 430060, China.

    Abstract

    OBJECTIVE:

    To explore whether PI3K/Akt/mdm2 signalling pathway affect the sensitivity of gastric cancer cell line SGC7901 cells to doxorubicin.

    METHODS:

    Gastric cancer cell line SGC7901 cells were exposed to doxorubicin and specific PI3K inhibitor wortmannin. Cell apoptosis was detected using flow cytometry. PI3K activity was detected by radioactive immunoprecipitation-kinase assay. Western blotting was employed to evaluate the expressions of PI3K-p85, pAkt-S473, Akt, pmdm2-S166 and p53.

    RESULTS:

    The level of apoptosis in gastric cancer SGC7901 cells treated with doxorubicin was gradually increasing. wortmannin enhanced its effects significantly. PI3K activity and the expression of pAkt-S473 increased in a time-dependent manner, pmdm2-S166, p53 were also increased wortmannin inhibited phosphorylation of mdm2 and improved the p53 expression.

    CONCLUSION:

    PI3K/Akt/mdm2 signalling pathway can be activated by doxorubicin and suppress apoptosis by promoting phosphorylation of mdm2. PI3K inhibitor wortmannin can enhance sensitivity of gastric cancer cells to chemotherapy.

    PMID:
    19062713
    [PubMed - indexed for MEDLINE]

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