药学学报, 2013, 48(6): 855-859
引用本文:
许秋菊, 侯莉莉, 胡国强, 谢松强. 麦冬皂苷B诱导人宫颈癌HeLa细胞自噬的机制[J]. 药学学报, 2013, 48(6): 855-859.
XU Qiu-ju, HOU Li-li, HU Guo-qiang, XIE Song-qiang. Molecular mechanism of ophiopogonin B induced cellular autophagy of human cervical cancer HeLa cells[J]. Acta Pharmaceutica Sinica, 2013, 48(6): 855-859.

麦冬皂苷B诱导人宫颈癌HeLa细胞自噬的机制
许秋菊, 侯莉莉, 胡国强, 谢松强*
(河南大学化学生物学研究所, 河南 开封 475004)
摘要:

 人宫颈癌HeLa细胞为研究对象, 探讨麦冬皂苷B的抗肿瘤作用及其分子机制。采用MTT检测、流式细胞仪分析、吖啶橙染色、Lyso-Tracker Red染色及HeLa-GFP-LC3转染细胞实验, 分别检测HeLa细胞的增殖、凋亡及自噬。结果表明, 麦冬皂苷B可抑制细胞增殖, 但并不诱导细胞凋亡, 可诱导细胞自噬, 并引起自噬标志性蛋白Beclin-1表达增加及LC3 I转变为LC3 II; 自噬抑制剂3-MA不但可以抑制该自噬作用而且几乎完全逆转其抗增殖作用, 提示其生长抑制作用为自噬依赖性的。Western blotting检测结果表明, 麦冬皂苷B抑制AKTmTORp70S6K的磷酸化并上调PTEN, 但并不引起Caspase 3的活化及PARP的切割。因此, 麦冬皂苷B抑制HeLa细胞增殖与凋亡无关, 而是通过抑制Akt/mTOR信号通路诱导其发生自噬。

关键词:   
Molecular mechanism of ophiopogonin B induced cellular autophagy of human cervical cancer HeLa cells
Abstract:

This study is to investigate the antitumor activity of ophiopogonin B (OP-B).  MTT assay, flow cytometric analysis, acridine orange staining, Lyso-Tracker Red staining and HeLa-GFP-LC3 transfect cells assay were used to detect the proliferation activity, apoptosis and autophagy of HeLa cells.  The results showed that OP-B exerted potent antiproliferative activity on HeLa cells, the cell growth inhibition effect of OP-B was not due to apoptosis and OP-B could induce autophagy of HeLa cells.  OP-B also induced the protein expression up-regulation of Beclin-1 and promoted LC3 I transformation LC3 II, which were representative proteins of autophagy.  Furthermore, 3-MA, an inhibitor of autophagy, not only inhibited OP-B-mediated autophagy but also almost completely reversed the antiproliferative effect of OP-B, suggesting that the growth inhibition effect of OP-B was autophagy dependent.  Western blotting demonstrated that OP-B inhibited the phosphorylation of Akt and its’ downstream vital protein, such as mTOR and p70S6K. In addition, OP-B also induced the protein expression up-regulation of PTEN, which is a negative regulation protein for Akt/mTOR signaling pathway.  However, OP-B did not affect the protein expression of total Akt.  Collectively, the antitumor effects of OP-B were autophagy-dependent via repression Akt/mTOR signaling pathway.  Therefore, OP-B is a prospective inhibitor of Akt/mTOR and may be used as an alternative compound to treat cervical carcinoma.

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