MK886在人结肠癌裸鼠模型中的抗血管生成作用

Anti-angiogenesis of MK886 in Nude Mouse Model of Human Colonic Cancer

目的通过动物体内实验研究5脂氧合酶活化蛋白(FLAP)抑制剂MK886对人结肠癌的抗血管形成作用,从而进一步探讨其抗肿瘤机制。方法将皮下接种HT-29人结肠癌细胞后建立人结肠癌模型的15只裸鼠随机分为三组,治疗组以MK886溶解在二甲基亚砜中投药;两对照组分别为投以二甲基亚砜和空白对照组。治疗一月后处死裸鼠并取瘤,用免疫组化方法检测各组肿瘤微血管密度,并比较结果。结果15只裸鼠全部成瘤,且实验过程中无一裸鼠死亡;免疫组化检测肿瘤微血管密度结果显示,两对照组肿瘤微血管密度差异无统计学意义(P>0.05),而治疗组肿瘤微血管密度显著低于两对照组(P<0.05)。结论MK886可通过抑制肿瘤微血管形成抑制人结肠癌的生长。

Objective To study the Anti-angiogenesis of the 5-1ipoxygenase activating protein（FLAP） inhibitor, MK886, on human colonic cancer in vivo and further explore its anti-tumor mechanism. Methods HT-29 humancolonic cancer cells were subcutaneously injected into the flanks of 15 nude mice to establish xenograft models. Fifteen mice were divided into three groups randomly. The mice in MK886-treated group were administered with MK886 dissolved into DMSO, and the mice in two control groups were treated with DMSO or nothing, respectively. After the treatment for one month, all nude mice were killed, and all tumors were removed. The microvessel density （MVD） of tumors was measured by using immunohistochemistry and the results were compared. Results None of the 15 nude mice died during the experiment and all nude mice formed in situ mass of colonic tumor. Immunohistochemistry, revealed that there was no significaut difference in MVD between two control groups, and the MVD in MK886-treated group was significantly decreased as compared with the control groups （P〈0. 05）. Conclusion 5-LOX inhibitor, MK886 inhibits the growth of colonic tumor by suppressing the angiogenesis of tumor.