Study on relationship between IGFBP-5/p53 axis and anti-proliferation effect of tetrandrine in MCF-7 cells / 中国药理学通报

ABSTRACT

Aim To study the effect of tetrandrine ( Tet ) on proliferation of MCF-7 breast cancer cells and the possible mechanism underlying this biological process. Methods CCK-8, flow cytometric and Western blot were introduced to analyze the effect of Tet on proliferation and apoptosis in MCF-7 cells.Re-al-time PCR and/or Western blot assay were employed to detect the effect of Tet on expression of IGFBP-5 , p53 and MDM2.CCK-8 and recombinant adenovirus were utilized to determine the effect of IGFBP-5 on the proliferation inhibitory effect of Tet .Western blot assay was introduced to evaluate the effect of IGFBP-5 on p53 which was induced by Tet .Results Tet inhibited the proliferation , arrested cell cycle at G 1 phase and decreased the expression of PCNA concentration dependently in MCF-7 cells.Meanwhile, Tet increased the percentage of apoptotic cells , the level of Bad and reduced the level of Bcl-2.Tet increased the expres-sion of IGFBP-5 either mRNA or protein , over-expres-sion of IGFBP-5 enhanced the anti-proliferation activity of Tet in MCF-7 cells, but knockdown of IGFBP-5 at-tenuated this effect of Tet .Tet increased the level of p53 and decreased that of MDM2, and exogenous IG-FBP-5 enhanced the effect of Tet on p53 and MDM2, respectively .Conclusion Tet can inhibit the prolifer-ation of MCF-7 cells, and this activity is partly media-ted by increasing the function of p 53 signal , which may be triggered by the Tet-induced IGFBP-5.