茶多酚对微卫星不稳定结直肠癌裸小鼠的抗肿瘤作用及其作用机制  

Anticancer effects of tea polyphenols on colorectal cancer with microsatellite instability in nude mice

作　　者：戴功建[1] 金黑鹰[2] 丁义江[2] 夏建国[1] 刘秀芳[2] 刘飞[2] 谈瑄忠[2] 耿建祥[2] 

机构地区：[1]南京医科大学第一附属医院胃肠外科,江苏南京210082 [2]南京中医药大学第三附属医院全国肛肠科医疗中心,江苏南京210001

出　　处：《中西医结合学报》2008年第12期1263-1266,共4页Journal of Chinese Integrative Medicine

基　　金：国家自然科学基金资助项目(No.30572447);南京市医学发展重点项目资助(No.ZKX05028);江苏省"科教兴卫工程"医学重点人才资助项目

摘　　要：目的:探索茶多酚对微卫星不稳定结直肠癌裸小鼠的作用及其作用机制。方法:采用hMSH2缺失结肠癌细胞株Lovo细胞建立裸鼠的皮下瘤模型,4周后使用皮下瘤接种法建立结肠造口结肠癌原位移植瘤模型。40只模型裸鼠分为模型组和50、75、100mg/kg茶多酚组。腹腔注射茶多酚治疗5d后,计算肿瘤抑制率,并检测肿瘤微卫星不稳定情况和转化生长因子β1(transforming growth factor-β1,TGF-β1)、TGF-β2和胰岛素样生长因子(insulin-like growth factor,IGF)片段的变化情况。结果:使用50、75和100mg/kg 3个剂量茶多酚治疗后,在1、2、3和4周末,治疗组和模型组肿瘤抑制率比较,差异有统计学意义(P<0.01);3个治疗组之间比较,差异无统计学意义。使用茶多酚治疗后肿瘤微卫星标志趋于稳定。结论:茶多酚对错配修复基因缺失的结直肠癌有明显抑制作用,其作用机制可能与抑制微卫星不稳定有关。Objective： To study the anticancer effects of tea polyphenols on colorectal cancer with microsatellite instability （MSI） in nude mice and to explore its mechanism. Methods： A colostomy was performed on the caecum of nude mice. Tumor fragments collected from the subcutaneous tumor of hMSH2-absence colon carcinoma Lovo cell line were surgically implanted onto the submucosaof the caecum during colostomy to establish the model. Then, the nude mice were divided into untreated group and 50, 75 and 100 mg/kg tea polyphenols groups. The mice in tea polyphenols-treated groups were given intra-abdominal injection of 50, 75 and 100 mg/kg tea polyphenols respectively. The inhibition rates of tumors were calculated, and microsatellite instability （MSI） and the alteration of transforming growth factor-β1 （TGF-β1）, TGF-β2 and insulin-like growth factor （IGF） were detected by Genescan method at different times after the injection. Results： The tumor volumes of the three groups began to decrease at the 1st week and decreased most greatly from 2 to 3 weeks after treatment, and then the tumors tended to increase. The study found that tea polyphenols could inhibit the tumor growth. The tumor inhibition rates in the three treated groups were significantly higher than those in untreated group 1, 2, 3 and 4 weeks after treatment （ P〈0.01）. Detection of MSI showed that the colorectal tumor in the untreated group presented with four MSI signs, including BAT- 25, D2S123, D5S346 and D178250, and TGF-β1, TGF-β2, IGF expressions. After using the tea polyphenols, the microsatellite tended to become stable. Conclusion： Tea polyphenols can inhibit the mismatch-repair-gene deficient colorectal cancer in nude mice by down-regulating the microsatellite instability.

关 键 词：茶多酚 DNA错配修复 基因缺失 结直肠癌 微卫星不稳定性 裸小鼠 

分 类 号：R735.35[医药卫生—肿瘤]