Abstract
PURPOSE: The objective of this study was to investigate the anti-tumor effects and analyze the mechanism of artesunate (ART) action on breast cancer in vivo using tumor transplanted nude mice. METHODS: The human breast tumor cell line MCF-7 was transplanted into nude mice, and the animals were treated with various doses of ART alone or in combination with cyclophosphamide (CTX) or normal saline (NS). The tumor inhibitory effects were observed and compared, and the ultrastructural morphology of the transplanted tumor cells was observed by electron microscopy. The apoptosis rates and cell cycle status were detected by flow cytometry (FCM). The expression of apoptosis-related proteins p53, Bcl-2, Bax and Caspase-3 were detected by immunohistochemistry and IGF-IR was detected by western blot. The expression correlation for these proteins was also analyzed. RESULTS: The tumor inhibition rates in the low dose ART group, high dose ART group, CTX group and combined drug therapy group were (24.39±10.20)%, (40.24±7.02)%, (57.01±5.84)% and (68.29±5.1)%, respectively. The cell cycle was arrested in phase G0/G1 after treatment with ART. The expression of Bcl-2 was significantly reduced, and the expression levels of Bax and Caspase-3 were significantly increased in the ART group compared to the negative control saline group. There was no significant difference detected in p53 expression. The Bcl-2 level was negatively related to Bax and Caspase-3. The western blotting results showed IGF-IR downregulation. CONCLUSIONS: ART inhibits the growth of MCF-7 breast tumor cell xenografts in nude mice. The anti-tumor mechanism of ART for human breast carcinoma in nude mice might be correlated with the alteration of apoptosis related protein expression, which may further induce apoptosis and inhibit cell proliferation.