Antitumor effects of Xi Huang pills on MDA-MB-231 cells in vitro and in vivo

作者：Zheng, Wenxian; Han, Shuyan; Jiang, Shantong; He, Xiran; Li, Xiaohong; Ding, Huirong; Cao, Minhua; Li, Pingping^*

来源：Molecular Medicine Reports, 2018, 18(2): 2068-2078.

DOI：10.3892/mmr.2018.9203

• Xi Huang pills
• antiproliferative activity
• apoptosis
• cell cycle
• MDA-MB-231
• triple-negative breast cancer

The management of patients with triple-negative breast cancer is challenging due to the lack of effective therapeutic options, aggressive behavior and relatively poor prognosis. Xi Huang pills (XHP) are a well-known traditional Chinese medicine that demonstrate anticancer activities. The aim of the present study was to investigate the antitumor effects of XHP on MDA-MB-231 cells in vitro and in vivo, and its potential underlying molecular mechanisms. In the present study, an MTT assay was used to evaluate the antiproliferative activity of XHP on MDA-MB-231 cells. In order to investigate the effects further, cell cycle distribution, apoptosis and mitochondrial membrane potential assays were performed, as well as western blot analyses. In addition, a tumor xenograft model was employed to investigate the effects of XHP in vivo. The results of the MTT assay demonstrated that the viability of MDA-MB-231 cells was markedly inhibited by XHP in a dose- and time-dependent manner. The inhibitory effect of XHP on the viability of MDA-MB-231 cells was greater when compared with MCF-10A cells. An increase in apoptosis and loss of mitochondrial membrane potential was observed following 4, 8 and 12 mg/ml XHP treatment of MDA-MB-231 cells. The protein expression levels of cleaved caspase-3 were increased by 1.62-, 2.13- and 2.19-fold, respectively, when compared with the untreated controls, whereas no effects on the expression of B-cell lymphoma 2 (Bcl-2) or Bcl-2-associated X protein (Bax) were observed. The results of the cell cycle distribution assay analysis demonstrated that XHP treatment arrested cells at the G(2)/M phase. In addition, XHP treatment decreased the expression of cyclin A and increased the expression of p21(Cip1). In vivo experiments revealed that XHP inhibited the growth of MDA-MB-231 xenograft tumors without body weight loss, and demonstrated similar effects on the protein expression levels of cleaved caspase 3, cyclin A and p21(Cip1) as observed in vitro. In conclusion, the viability of MDA-MB-231 cells was inhibited by XHP in a dose-dependent, time-dependent and cell-selective manner in vitro, and the potential underlying mechanisms may involve apoptosis and cell cycle arrest at the G(2)/M phase. XHP may induce apoptosis in MDA-MB-231 cells via the intrinsic pathway, which does not involve the Bcl-2/Bax ratio. G(2)/M phase arrest may have been due to the integrated action of decreased cyclin A expression and increased p21(Cip1) expression. In addition, XHP inhibited the growth of xenograft tumors in the absence of body weight loss in vivo.

• 出版日期2018-8
• 单位北京大学