Efficacy of MK886 in Nude Mouse Model of Human Colonic Cancer
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Graphical Abstract
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Abstract
Objective To investigate the effect of the FLAP inhibitor, MK886 on human colonic cancer xenograf t s in vi vo and to explore it s potential anti2neoplasm mechanism. Methods Cultured HT229 hu2 man colonic cancer cells were injected into the flanks of fif teen nude mice to develop xenograf t models and the tumor2bearing nude mice were randomized into three groups to be administered with MK886 dissolved into DMSO, DMSO only, nothing, respectively. The mice were monitored for 4 consecutive weeks for tumor volume changes. Then the tumor tissues was isolated and weighted, followed by pathological exam2 ination. The expression of 52LOX in tumor tissue was detected by immunohistochemist ry and apoptosis of colonic cancer cells was also detected by TUNEL. Results None of the 15 nude mice died during the ex2 periment and all nude mice formed in situ mass of colorectal tumor. MK886 inhibited growth of human HT29 colon cancer xenograf t s in athymic mice, measured as both tumor volume and tumor weight . The expression of 52LOX in tumor tissue of cont rol group was st ronger than that of t reated groups. This test also confirmed the induction of apoptosis in colonic cancer cells and the function of inhibiting angiogenesis of tumor by MK886. Conclusion 52LOX inhibitor, MK886 inhibit s the growth of colonic tumor by indu2 cing the apoptosis of human colonic cancer cells and inhibiting the angiogenesis of tumor.
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