目的：探讨水飞蓟宾对胃癌细胞缺氧诱导因子1α（HIF-1α）表达的影响及其可能的分子机制。方法： 低氧条件下体外培养胃癌细胞系MGC803，用不同浓度水飞蓟宾处理后，分别采用Real-time PCR和Western blotting法检测HIF-1α mRNA、蛋白的表达以及mTOR和Akt的磷酸化水平，MTT法检测水飞蓟宾对MGC803细胞增殖的影响。结果： 细胞低氧状态下生长4 h后，与正常氧浓度组相比，细胞内HIF-1α蛋白表达水平显著增高[（0.94±0.16）vs（0.015±0.03），P<0.01）]；经250 μmol/L水飞蓟宾处理后，与处理前相比，HIF-1α蛋白表达水平明显减少[（0.24±0.09）vs（0.94±0.16），P<0.01]。与正常氧浓度组相比，低氧并不能增加HIF-1α mRNA的表达[（0.074±0.011） vs （0.07±0.02），P>0.05]，即便加入250 μmol/L水飞蓟宾处理对HIF-1α mRNA的表达也无明显影响[（0.081±0.011） vs （0.07±0.02），P>0.05]，但水飞蓟宾能显著增加泛素化HIF-1α蛋白的表达[（0.94±0.16）vs（0.24±0.09），P<0.01]；水飞蓟宾处理后能明显抑制mTOR磷酸化水平[（0.17±0.06） vs （0.53±0.14），P<0.05）]，并能明显抑制MGC803细胞的增殖[（52.94±6.15） vs （100±3.22），P<005）]。与处理前相比，50和100 μmol/L水飞蓟宾处理对Akt磷酸化无明显影响[（0.16±0.09）、（0.17±0.06） vs （011±0.04），P>0.05]，但250 μmol/L水飞蓟宾处理后，细胞内Akt磷酸化水平明显增强[（0.33±0.06）vs（0.11±0.04），P<005]。结论： 水飞蓟宾可能通过影响mTOR和HIF-1α的表达水平而发挥抗肿瘤活性。

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 ([094±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±009], [0.17±006] 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.

国家自然科学基金资助项目（No.81372894）