采用人肿瘤类器官研究阻断Wnt信号治疗大肠癌的可行性  

Feasibility of human tumor-like organ studying the inhibition of wnt signal in the treatment of colorectal cancer

作　　者：查娟民[1] 林倩[1] 李华善 何伟奇[1] 周秀敏[1] 

机构地区：[1]苏州大学附属第一医院肿瘤科,江苏苏州215006

出　　处：《中国现代医生》2016年第27期5-8,共4页China Modern Doctor

基　　金：国家自然科学基金资助项目(81200620;31401229);江苏省自然科学基金资助项目(BK20140319)

摘　　要：目的建立和优化大肠癌患者肿瘤类器官培养体系,为研究阻断Wnt信号治疗大肠癌提供新模型。方法选择大肠癌患者18例,收集癌组织及癌旁组织配对标本。采用定量PCR测定癌组织和癌旁组织Wnt3 m RNA和肠干细胞标记分子Lgr5、Ascl2的表达水平。术中采集肿瘤组织,使用类器官培养基培养肿瘤类器官。使用Wnt信号抑制剂IWP-2处理肿瘤类器官,观察IWP-2对肿瘤类器官形态、生长等的影响。结果定量PCR表明,与癌旁组织相比,肿瘤组织中的Wnt3表达水平较高[分别为(1.00±0.08)和(2.99±0.27),P<0.01]。癌旁组织和肿瘤组织Lgr5[分别为(1.00±0.05)和(5.63±1.80),P<0.01)]、Ascl2[分别为(1.00±0.39)和(4.03±0.33),P<0.05]的表达水平也较高。IWP-2处理可显著抑制肿瘤类器官生长[未处理和处理后类器官面积分别为(10.02±1.34)×10~4m^2和(2.97±0.62)×10~4m^2,P<0.01]。结论Wnt信号通路激活和大肠癌发生密切相关,抑制Wnt信号可有效抑制肿瘤细胞生长,可能是治疗大肠癌的一种有效方法。肿瘤类器官可以作为筛选大肠癌治疗药物的一种模型。Objective To establish and optimize a tumor-like organ culture system in the patients with colorectal can- cer and to provide a new model for the study of inhibiting Wnt signaling in the treatment of colorectal cancer. Methods 18 patients with colorectal cancer were selected, and matched specimens of cancer tissues and para-careinoma tissues were collected. The expression levels of Wnt3 mRNA and marker molecules of intestinal stem cells of Lgr5 and Ascl2 in cancer tissues and para-carcinoma tissues were determined by quantitative PCR. Tumor tissue was harvested during the operation, and tumor-like organs were cultured in organ-like medium. The effect of IWP-2 on the morphology and growth of tumor-lille organs was observed by using Wnt signaling inhibitor IWP-2 for tumor-like organs. Results It was shown by quantitative PCR that Wnt3 expression was higher in tumor tissues than that in para-careinoma tissues （1.00±0.08, and 2.99±0.27, respectively, P〈0.01）. The expression level of LgrS[（1.0±0.05） and （5.63±1.80）, P〈0.01, respectively] and Asc12[（1.00±0.39） and （4.03±0.33）, P〈0.05] was also higher in the para-carcinoma tissues and tumor tissues, the growth of tumor-like organs [（10.02±1.34）×10 4 m2 and（2.97±0.62） ×10 4 m2, P〈0.01] were significantly inhibited by IWP-2 treatment. Conclusion The activation of Wnt signaling pathway is closely related to the development of colorectal carcinoma. Inhibition of Wnt signaling can effectively inhibit the growth of tumor cells, which may be an effective method for the treatment of colorectal cancer. Tumor-like organs can be used as a model of drug for colorectal cancer.

关 键 词：大肠癌 类器官 WNT信号 抑制剂 

分 类 号：R735.3[医药卫生—肿瘤]