裸鼠结肠癌肝转移模型中多韦替尼抗肿瘤作用的研究

Anti-tumor of the dovitinib on liver metastasis of colon cancer nude mice model

目的建立稳定的裸鼠结肠癌肝转移模型,观察多韦替尼(TKI-258)药物的肿瘤抑制作用。方法将人结肠癌细胞株Lo Vo接种于裸鼠脾脏建立异位肝转移模型,随机分为TKI-258研究组和对照组。研究组TKI-258灌胃,对照组同一时间段用生理盐水。采用形态学和病理学方法比较TKI-258研究组与对照组间肝转移癌形成情况,并对TKI-258研究组肝转移的预防与治疗进行评价和鉴定。结果裸鼠结肠癌异位肝转移模型的成瘤率为100%。TKI-258研究组与对照组相比抑制肝转移癌的形成,肝转移评分也明显下降,差异有显著性意义(P<0.05)。TKI-258研究组的肝转移癌明显缩小,浸润深度变浅,部分有治愈瘢痕,两组差异在形态学上有显著性意义(P<0.05)。TKI-258研究组的肿瘤中央细胞坏死及细胞凋亡成片,只存留边缘部分肿瘤细胞,细胞分布不规则,两组在显微镜下观察差异有显著性意义(P<0.05)。结论异位肝转移模型适合对肝转移率和取材要求较高的实验研究。TKI-258对裸鼠肝转移癌的预防和治疗有一定的疗效,能有效抑制转移癌的形成,但有必要进行临床试验来证实其量化效果。

Objective To establish a feasible and stable liver metastasis model of human colon cancer in nude mice.Ob-serve of dovitinib （TKI-258） anti-tumor effect in liver metastasis model of human colon cancer.Methods Human colon cancer cell line LoVo were injected into spleen of nude mouse by ectopic implantation to establish the liver metastasis model of human colon cancer.The tumor-bearing nude mice were randomized into two groups, TKI-258 study group and con-trol group.TKI-258 was force-fed （ gavage） to study group and control group, evaluating tumor formation, growth effi-ciency and liver metastasis via morphological and histopathological examination.Results The tumor formation rate was 100% of liver metastasis of colon cancer in nude mice by ectopic implantation.TKI-258 group inhibited the liver metasta-sis compared with the control group with a statistically significance （P〈0.05）.There were marked morphological differ-ence of liver metastasis between TKI-258 group and control group, which the liver metastasis of TKI-258 group was com-parably narrowed, infiltration depth became shallowed with some cured scars （P〈0.05）.In addition, the liver metastasis of TKI-258 group was microscopically distinct from the control group, on which exhibited irregularly distributed cells in the edge of the tumor with cell necrosis and apoptosis in the center （P〈0.05）.Conclusion This liver metastasis model of human colon cancer facilitates the preclinical research and assessment requiring high rates of liver metastasis and liver tumor formation.Moreover, TKI-258 group may have certain curative effects on prevention and treatment for liver metasta-sis model of human colon cancer in nude mice by ectopic implantation, and may has significant restraining effect on the tumor formation, which remains clinical trials to confirm the quantitative effects.