Inhibitory Effects of Evodiamine on in Vitro Invasion and Experimental Lung Metastasis of Murine Colon Cancer Cells.

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Abstract
We have previously reported that evodiamine had a marked inhibitory activity on tumor cell migration in vitro. To extend our study, the effects of evodiamine on invasion, growth, and metastatic development of colon 26-L5 cells were examined here. Evodiamine inhibited the invasion of tumor cells into Matrigel in a concentration-dependent manner, and achieved 70% inhibition at 10 microg/ml. Treatment of tumor cells with evodiamine for 24 h showed little effect on tumor growth at concentrations of less than 10 microg/ml, whereas an over 48-h treatment resulted in a concentration- and time-dependent inhibition. Pretreatment of tumor cells with 10 microg/ml evodiamine before inoculation into mice caused 70% reduction in their lung metastasis formation. When evodiamine at 10 mg/kg was administered into mice from the 6th day after tumor inoculation, the number of tumor nodules in lungs was decreased by 48% as compared to control. The inhibition rate was equivalent to that produced by cisplatin, a potent anti-cancer drug. Evodiamine did not affect the body weight of mice in the experimental period, whereas cisplatin caused serious weight loss. These results suggest that evodiamine may be regarded as a promising agent in tumor metastasis therapy.