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Abstract

The Potential Applications of the Potent Cytotoxic Ansamitocin P-3 in the Treatment of Gastric Carcinoma

Shilei Wang, Jinlei Ye, Ying Chen, Zhilei Cui, Qiping Zheng, Songhai Shen and Lichun Sun

Gastric carcinoma is a refractory disease that seriously threatens human health globally. Unfortunately, its mortality is still high among common cancers. In order to develop a new type of anti-gastric cancer drug and avoid side effects of traditional chemotheray, a new drug-targeting strategy was considered in our studies. We firstly selected certain classic cytotoxic compounds such as ansamitocin P-3 (AP-3), colchicine and paclitaxel and investigated their efficacy in the suppression of gastric cancer cell growth and tumor growth. We found that these compounds displayed their potent suppressive activities. Particularly, AP-3 showed its significant tumor suppression in xenograft mouse model, and was also observed with its severe side effects. The results supported that AP-3 itself most likely was not druggable, but might be applied for drug conjugates via coupling it to a drug delivery vehicle to enhance its anti-tumor efficacy and reduce its side effects.