5-脂氧合酶活化蛋白抑制剂MK886治疗裸鼠人结肠癌移植瘤的实验

Efficacy of MK886 in Nude Mouse Model of Human Colonic Cancer

目的观察5-脂氧合酶活化蛋白(FLAP)抑制剂MK886对裸鼠人结肠癌移植瘤的治疗作用,并探讨其抗肿瘤的可能机制。方法以HT-29人结肠癌细胞制备裸鼠人结肠癌移植瘤模型,15只荷瘤裸鼠随机分为三组,治疗组以MK886溶解在二甲基亚砜中投药,两对照组分别给以二甲基亚砜及不作任何治疗。治疗期间观察肿瘤生长情况,治疗结束后处死裸鼠并取瘤,测量肿瘤体积重量,用免疫组化方法检测肿瘤微血管密度,用TUNEL法检测肿瘤细胞凋亡情况。结果15只裸鼠全部成瘤,且实验过程中无一裸鼠死亡;通过测量瘤体积、瘤重结果显示,MK886可抑制人结肠癌裸鼠皮下移植瘤的生长;实验还证实MK886对人结肠癌裸鼠皮下移植瘤具有诱导肿瘤细胞凋亡及抗血管生成作用。结论MK886对于裸鼠人结肠癌移植瘤具有明显的治疗效果,MK886可能通过诱导肿瘤细胞凋亡、抑制肿瘤微血管形成等机制控制人结肠癌的生长。

Objective To investigate the effect of the FLAP inhibitor, MK886 on human colonic cancer xenografts in vivo and to explore its potential anti-neoplasm mechanism. Methods Cultured HT-29 human colonic cancer cells were injected into the flanks of fifteen nude mice to develop xenograft models and the tumor-bearing 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 examination. The expression of 5-LOX in tumor tissue was detected by immunohistochemistry and apoptosis of colonic cancer cells was also detected by TUNEL. Results None of the 15 nude mice died during the experiment and all nude mice formed in situ mass of colorectal tumor. MK886 inhibited growth of human HT29 colon cancer xenografts in athymic mice, measured as both tumor volume and tumor weight. The expression of 5-LOX in tumor tissue of control group was stronger than that of treated groups. This test also confirmed the induction of apoptosis in colonic cancer cells and the function of inhibiting angiogenesis of tumor by MK886. Conclusion 5-LOX inhibitor,MK886 inhibits the growth of colonic tumor by inducing the apoptosis of human colonic cancer cells and inhibiting the angiogenesis of tumor.