TGF-β1/PTEN/PI3K signaling plays a critical role in the anti-proliferation effect of tetrandrine in human colon cancer cells

  • Authors:
    • Qian-Zhao Chen
    • Yang Li
    • Ying Shao
    • Yu-Hua Zeng
    • Wen-Yan Ren
    • Rong-Xing Liu
    • Lin-Yun Zhou
    • Xue-Lian Hu
    • Ming Huang
    • Fang He
    • Wen-Juan Sun
    • Ke Wu
    • Bai-Cheng He
  • View Affiliations

  • Published online on: February 13, 2017     https://doi.org/10.3892/ijo.2017.3875
  • Pages: 1011-1021
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Abstract

The diagnosis and treatment for colon cancer have been greatly developed, but the prognosis remains unsatisfactory. There is still a great clinical need to explore new efficacious drugs for colon cancer treatment. Tetrandrine (Tet) is a bis-benzylisoquinoline alkaloid. It has been shown that Tet may be a potential candidate for cancer treatment, but the explicit mechanism underlying this activity remains unclear. In this study, we investigated the anticancer activity of Tet in human colon cancer cells and dissected the possible mechanism. With cell viability assay and flow cytometry analysis, we confirmed that Tet can effectively inhibit the proliferation and induce apoptosis in HCT116 cells. Mechanically, we found that Tet greatly increases the mRNA and protein level of TGF-β1 in HCT116 cells. Exogenous TGF-β1 enhances the anti-proliferation and apoptosis inducing effect of Tet in HCT116 cells, which has been partly reversed by TGF-β1 inhibitor. Tet decreases the phosphorylation of Akt1/2/3 in HCT116 cells. This effect can be enhanced by exogenous TGF-β1, but partly reversed by TGF-β1 inhibitor. Tet exhibits no effect on total level of PTEN, but decreases the phosphorylation of PTEN; exogenous TGF-β1 enhances the effect of Tet on decreasing the phosphorylation of PTEN, which was partly reversed by TGF-β1 inhibitor. Our findings suggested that Tet may be a promising candidate for colon cancer treatment, and the anticancer activity may be mediated by inactivating PI3K/Akt signaling through upregulating TGF-β1 to decrease the phosphorylation of PTEN.
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March-2017
Volume 50 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Copy and paste a formatted citation
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Spandidos Publications style
Chen Q, Li Y, Shao Y, Zeng Y, Ren W, Liu R, Zhou L, Hu X, Huang M, He F, He F, et al: TGF-β1/PTEN/PI3K signaling plays a critical role in the anti-proliferation effect of tetrandrine in human colon cancer cells. Int J Oncol 50: 1011-1021, 2017.
APA
Chen, Q., Li, Y., Shao, Y., Zeng, Y., Ren, W., Liu, R. ... He, B. (2017). TGF-β1/PTEN/PI3K signaling plays a critical role in the anti-proliferation effect of tetrandrine in human colon cancer cells. International Journal of Oncology, 50, 1011-1021. https://doi.org/10.3892/ijo.2017.3875
MLA
Chen, Q., Li, Y., Shao, Y., Zeng, Y., Ren, W., Liu, R., Zhou, L., Hu, X., Huang, M., He, F., Sun, W., Wu, K., He, B."TGF-β1/PTEN/PI3K signaling plays a critical role in the anti-proliferation effect of tetrandrine in human colon cancer cells". International Journal of Oncology 50.3 (2017): 1011-1021.
Chicago
Chen, Q., Li, Y., Shao, Y., Zeng, Y., Ren, W., Liu, R., Zhou, L., Hu, X., Huang, M., He, F., Sun, W., Wu, K., He, B."TGF-β1/PTEN/PI3K signaling plays a critical role in the anti-proliferation effect of tetrandrine in human colon cancer cells". International Journal of Oncology 50, no. 3 (2017): 1011-1021. https://doi.org/10.3892/ijo.2017.3875