Objective: To investigate the effects of Chinese herbal formula Qinghuofu (QHF) on the migration and invasion of breast cancer MCF-7 cells and its possible molecular mechanisms, thereby providing a theoretical basis to find effective anti-cancer medicine and therapeutic targets for the treatment of anti-migration and anti-invasion of breast cancer. Methods: Breast cancer MCF-7 cells were treated with different QHF and other different reagents, CCK8 assay was used to detect the influence of the reagents on the proliferation of MCF-7 cells; Scrape migration and Transwell assay were used to quantitatively determine the migration and invasion effects of QHF and HGF on the MCF-7 cells. Subsequently, the c-Met inhibitor and its downstream ERK and PI3K inhibitors were used to investigate the relationship between the migration and invasion of MCF-7 cells, as well as its downstream MAPK/ERK and PI3K/Akt signaling pathways. The expression levels of HGF, c-Met, ERK, p-Akt, p-c-Met, p-ERK, p-Akt, MMP2, MMP9, and VEGF in breast cancer MCF-7 cells treated with QHF and other reagents were also examined. Results: The result indicated that formula QHF not only significantly inhibited the proliferation of MCF-7 cells, but also significantly suppressed the effects of (hepatocyte growth factor) HGF (40 ng/mL) on the proliferation and movement of MCF-7 cells, reducing the ability of the cells to invade and migrate. Western blot analysis indicated that QHF and c-Met inhibitor significantly decreased the expression of p-c-Met, p-ERK1, p-ERK2, p-Akt, MMP-2, MMP-9, and VEGF, while HGF could significantly increase the expression of p-c-Met in MCF-7 cells; c-Met downstream ERK and PI3K inhibitors could also significantly decreased the expression of MMP-2, MMP-9, and VEGF in MCF-7 cells; But the difference among c-Met, PI3K, ERK, and QHF group were not statistically significant. Conclusion: QHF can prevent the proliferation, migration, and invasion of MCF-7 cells by inhibiting the HGF/c-Met and its downstream PI3K/Akt and MAPK/ERK signaling pathways; Thereby down-regulating the expresssion of HGF, p-Met, p-ERK1, p-ERK2, p-Akt, MMP-2, MMP-9, and VEGF.
关键词:
乳腺癌;中药QHF复方;转移;HGF/c-Met信号通路;侵袭
Keywords:
Project Supported:
Natural Science Foundation of Hubei (no. 81573659)
Wei Hu, Dan Liu, Liang-bo Jiao, Wen Zhang, Xiang-yang Hu, Shen-tong Gan, Xin-yi Wang, Tao Chen. Mechanism of Chinese herbal formula QHF against breast cancer MCF-7 cells invasion and migration[J]. Chinese Herbal Medicines (CHM),2018,10(4):405-410
