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Silibinin inhibits mTOR phosphorylation and HIF-1α expression in gastric carcinoma cells under hypoxic condition
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Abstract:
Objective:To investigate the effect of Silibinin on hypoxia inducible factor-1α (HIF-1α) expression as well as its possible molecular mechanism. Methods：Gastric carcinoma cell line MGC803 was cultured in vitro under hypoxic condition. After treated with different concentration of Silibinin, the expression of HIF-1α mRNA was detected by Real-time PCR; HIF-1α protein level and phosphorylation of mTOR and Akt were detected by Western blotting. Effect of Silibinin on proliferation of MGC803 cell was analyzed by MTT assay. Results：After 4 h of incubation under hypoxia condition, the expression of HIF-1α protein was significantly increased in MGC803 cells, as compared with the normoxia group ([094±0.16] vs[0.015±0.03], P<0.01). After treatment with 250μmol/L Silibinin, the expression of HIF-1α protein was significantly inhibited as compared to pre-treatment ([0.24±0.09] vs [0.94±0.16], P<0.01). As compare with normoxia group, hypoxia couldn’t increase expression of HIF-1α mRNA ([0.074±0.011] vs [0.07±0.02], P>0.05), even though treatment with 250 μmol/L aqueous Silibinin also couldn’t significantly affect expression of HIF-1α mRNA ([0.081±0.011] vs[0.07±0.02], P>0.05) , but Silibinin could significantly increase the expression of ubiquitinated HIF-1α protein ([0.94±0.16] vs[0.24±0.09], P<0.01). After incubation with Silibinin, phosphorylation of mTOR was significantly inhibited ([0.17±0.06) vs [0.53±0.14], P<0.05), and proliferation of MGC803 cell was significantly inhibited ([52.94±6.15] vs [100±3.2]，P<0.05), as compared with pre-treatment. In contrast, 50 and 100 μmol/L Silibinin had no obvious effect on phosphorylation of Akt ([0.16±009], [0.17±006] vs [0.11±0.04], P<0.05), but 250 μmol/L Silibinin could significantly increase the phosphorylation of Akt in the cells ([0.33±0.06] vs [0.11±0.04], P<0.05). Conclusion：Silibinin could exert antitumor action through to effect on expression of mTOR and HIF-1α.
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Project Supported:
Project supported by the National Natural Science Foundation of China（No.81372894）
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