Scutellarin Inhibits Proliferation, Invasion, and Tumorigenicity in Human Breast Cancer Cells by Regulating HIPPO-YAP Signaling Pathway
Lengchen Hou, Lei Chen, Lin Fang
Department of Thyroid and Breast Surgery, Shanghai 10th People’s Hospital, Clinical College of Nanjing Medical University, Shanghai, China (mainland)
Med Sci Monit 2017; 23:5130-5138
The present study aimed to investigate the effects of Scutellarin on proliferation, invasion and tumorigenicity in human breast carcinoma MCF-7 cells and its associated molecular mechanisms.
MATERIAL AND METHODS: The MCF-7 cells were cultured with varies of concentrations of Scutellarin in vitro. The proliferation, invasion, and apoptosis of MCF-7 cells were studied via CCK-8 assay, transwell assay, and flow cytometry. In vivo expression of the HIPPO pathway key proteins YAP and p-YAP of MCF-7 cells were analyzed by immunohistochemistry.
RESULTS: The inhibition rates of Scutellarin-treated MCF-7 cells were 40.1%, 58.7%, and 70.6% for 24, 48, and 72 h, respectively. The MCF-7 cell proliferation was significantly inhibited by Scutellarin. Treating MCF-7 cells with Scutellarin led to invasion inhibition. The rates apoptotic cells were between 12.4±1.9% and 23.9±2.1% in 40–120 µM Scutellarin-administrated groups, which had a significant rise compared with the control group (7.8±1.9%, P<0.05). Scutellarin significantly inhibited MCF-7 xenograft tumor growth. Immunohistochemical analysis showed that the inhibition of tumor growth in Scutellarin-treated mice was associated with increased p-YAP and decreased YAP expression in vivo.
CONCLUSIONS: Scutellarin-treated breast carcinoma MCF-7 cells had significantly inhibited growth and induced apoptosis, which is associated with induction of autophagy through regulation of the HIPPO-YAP signaling pathway, providing support to the clinical use of Scutellarin-based medication to achieve optimized outcome in patients with breast carcinoma.
Keywords: Apoptosis, Breast Neoplasms, Cell Proliferation, Neoplasm Invasiveness