中国药理学通报2017，Vol.33Issue(9)：1227-1234,8.DOI:10.3969/j.issn.1001-1978.2017.09.009
汉防已甲素抑制人结肠癌细胞增殖与TGF-β1的关联机制研究
Relationship between anti-proliferationeffect of tetrandrine and TGF-β1 in human colon cancer cells
摘要
Abstract
Aim To study the relationship between the anti-proliferation effect of tetrandrine(Tet) and TGF-β1 in human colon cancer cells.Methods Cell viability assay, Western blot, flow cytometry and Annexin Ⅴ-EGFP staining were introduced to analyze the anti-cancer effect of Tet on HCT116 cells.Real-time PCR, Western blot,cell viability and immunofluorescent were employed to determine the relationship between the anti-cancer effect of Tet and TGF-β1 in HCT116 cells, the relationship between the anti-cancer effect of Tet and PI3K/Akt on HCT116 cells, and how TGF-β1 mediated the anti-cancer effect of Tet on HCT116 cells.Results Compared with the control groups, Tet apparently inhibited the proliferation, and induced cell cycle arrest at G1 phase and apoptosis in HCT116 cells.Tet greatly up-regulated the expression of TGF-β1 either the mRNA or protein level, and exogenous expression of TGF-β1 potentiated the anti-cancer effect of Tet in HCT116 cells, while TGF-β1 inhibitor attenuated it notably.Tet decreased the phosphorylation of Akt1/2/3, but no apparent effect was observed on total protein level of Akt1/2;PI3K inhibitor enhanced the anti-cancer effect of Tet in HCT116 substantially.Exogenous expression of TGF-β1 enhanced the Tet-induced decrease phorphorylation of Akt1/2/3, which was partly reversed by TGF-β1 inhibitor in HCT116 cells.Meanwhile, knockdown of PTEN elevated the level of phorphorylated Akt1/2/3, which was abolished by the exogenous expression of TGF-β1 in HCT116 cells.Conclusion Tet may be a potent candidate drug for colon cancer treatment, and the anti-cancer effect of Tet may be partly mediated by up-regulating TGF-β1 to inactivate PI3K/Akt signal.关键词
汉防已甲素/结肠癌/HCT116细胞/TGF-β1/PI3K/Akt/PTENKey words
tetrandrine/colon cancer/HCT116 cells/TGF-β1/PI3K/Akt/PTEN分类
医药卫生引用本文复制引用
任文艳,陈前昭,周林云,邵英,廖云鹏,王涵,朱茄慧,何百成..汉防已甲素抑制人结肠癌细胞增殖与TGF-β1的关联机制研究[J].中国药理学通报,2017,33(9):1227-1234,8.基金项目
国家自然科学基金资助项目(No 81572226) （No 81572226）
