BMP9 mediates the anticancer activity of evodiamine through HIF-1α/p53 in human colon cancer cells
BMP9 mediates the anticancer activity of evodiamine through HIF-1α/p53 in human colon cancer cells
复制标题
BMP9 通过 HIFα1α/p53 在人结肠癌细胞中介导吴茱萸碱的抗癌活性
DOI：
10.3892/or.2019.7427
复制
发表时间：
2020-02-01
期刊：
影响因子：
4.2
通讯作者：
Shu, De-Zhong
中科院分区：
文献类型：
--
作者：
Li, Fu-Shu;Huang, Jun;Shu, De-Zhong
Colon cancer is one of the most common malignancies. Although there has been great development in treatment regimens over the last few decades, its prognosis remains poor. There is still a clinical need to find new drugs for colon cancer. Evodiamine (Evo) is a quinolone alkaloid extracted from the traditional herbal medicine plant Evodia rutaecarpa. In the present study, CCK-8, flow cytometry, reverse transcription quantitative polymerase chain reaction, western blot analysis and a xenograft tumor model were used to evaluate the anti-cancer activity of Evo in human colon cancer cells and determine the possible mechanism underlying this process. It was revealed that Evo exhibited prominent anti-proliferation and apoptosis-inducing effects in HCT116 cells. Bone morphogenetic protein 9 (BMP9) was notably upregulated by Evo in HCT116 cells. Exogenous BMP9 potentiated the anti-cancer activity of Evo, and BMP9 silencing reduced this effect. In addition, HIF-1 alpha was also upregulated by Evo. The anticancer activity of Evo was enhanced by HIF-1 alpha, but was reduced by HIF-1 alpha silencing. BMP9 potentiated the effect of Evo on the upregulation of HIF-1 alpha, and enhanced the antitumor effect of Evo in colon cancer, which was clearly reduced by HIF-1 alpha silencing. In HCT116 cells, Evo increased the phosphorylation of p53, which was enhanced by BMP9 but reduced by BMP9 silencing. Furthermore, the effect of Evo on p53 was potentiated by HIF-1 alpha and reduced by HIF-1 alpha silencing. The present findings therefore strongly indicated that the anticancer activity of Evo may be partly mediated by BMP9 upregulation, which can activate p53 through upregulation of HIF-1 alpha, at least in human colon cancer.
