期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 863, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2019.172667
关键词
Shikonin; Breast cancer; Estrogen receptor; G protein-coupled estrogen receptor
资金
- National Natural Science Foundation of China [81273887, 81673764]
- Beijing University of Chinese Medicine Research and Development Fund [2017-ZXFZJJ-005]
- 111 Project [B07007]
Estrogen receptor (ER) is expressed in most Breast cancer (BC) patients. G protein-coupled estrogen receptor (GPER), which is a membrane-bound estrogen receptor, is associated with the tumor development and progression in BC. Shikonin (SK) is a natural compound that is known to have anti-tumor effects. This study aims to assess the effects of shikonin on the cell proliferation, cell cycle and cell apoptosis of BC and whether the effects are related to ER/GPER signaling pathway. The results demonstrated that shikonin inhibited the cellular proliferation of MCF-7 BC cells via G(0)/G(1) arrest and apoptosis in concentration-dependent manner. The anti-proliferative effect of SK on SK-BR-3 BC cells was associated with apoptosis. Both ER alpha and GPER were expressed in MCF-7 cells, while ER alpha were negative and GPER were positive in SK-BR-3 cells. Furthermore, shikonin downregulated the expression of ER alpha and GPER, and this effect was not affected by the estrogen environment. In addition, shikonin downregulated the EGFR and p-ERK expression in MCF-7 and SK-BR-3, which was also not affected by the estrogen environment. EGFR and p-ERK were still suppressed by co-treatment with the selective GPER against G1 or antagonist G15. In conclusion, these results suggest that shikonin shows anti-tumor effects on MCF-7 and SK-BR-3 cells. The effects seem to be associated with EGFR/p-ERK downregulation via ERa and GPER inhibition.
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