白细胞介素10和转化生长因子β1与小鼠结肠癌肝转移的关系

Correlation of IL-10 and TGF-β1 expression with the liver metastasis of colon carcinoma in mice

目的了解小鼠脾脏接种结肠癌细胞发生肝转移所需肿瘤细胞数的临界值，探讨白细胞介素10（IL-10）和转化生长因子β1（TGF-β1）在结肠癌肝转移过程中的作用及意义。方法选择6-8周雌性Balb／c小鼠36只，随机分为6组，各6只。实验组通过脾脏注射小鼠结肠癌CT26细胞建立小鼠结肠癌肝转移模型，注射细胞数分别为1×10^5个（A组）、5×10^4个（B组）、1×10^4个（C组）、5×10^2个（D组）和1×10^3个（E组），对照组为正常小鼠。于术后21天处死小鼠，肉眼观察肝脏肿瘤转移情况并行肝脏组织学观察及IL-10和TGF-β1免疫组织化学染色。结果A、B组小鼠肝脏转移率均为100％，其他各组小鼠均未见有肝转移瘤形成。IL-10和TGF-β1表达在对照组均为阴性，但在各实验组小鼠肝脏表达均为阳性，且表达量随着脾脏注射CT26细胞数量的增加而升高，IL-10和TGF-β1的表达量在A、B、C组与D组或E组间比较，差异均有统计学意义（P=0．000），但在D、E两组间比较，差异无统计学意义。结论5×10^4个CT26细胞脾脏注射可成功建立小鼠结肠癌肝转移模型；CT26细胞可诱导肝脏产生IL-10和TGF-β1,IL-10和TGF-β1可促使结肠癌肝转移瘤的形成。

Objective To learn about the number of colon carcinoma cells that could develop to liver metastasis by injecting colon carcinoma cells （CT26 cells） into spleen of mice. To explore the role and significance of IL-10 and TGF-β1 during the liver metastasis of colon carcinoma. Methods Thirty- six female, six-to-eight week old, Balb/c mice were selected and divided into six groups at random. Experimental groups were established by injecting CT26 cells into the spleen, with the cells number： 1 × 10^5 （group A）, 5× 10^4 （group B）, 1 ×10^4 （group C）, 5 ×10^3 （group D） and 1 ×10^3 （group E）. All mice were killed at 21 days post-operation. The liver metastases conditions were observed directly and liver tissues were analyzed for IL-10 and TGF-β1 expression using immunohistochemistry. Results The percentage of liver metastases was 100% in the group A and group B, no liver metastases happened in the other groups. IL-IO and TGF-β1 expression was negative in the liver of normal mice, while positive in the the experiment groups. The expression levels of IL-10 and TGF-β1 were increased with number of tumor cells, there were significantly different between group A, B, C and group D, E （P = 0.000）, but no difference was found between group D and group E. Conclusions liver metastases of colon carcinoma model in mice can be successfully established with spleen injection of 5 ×10^4 colon carcinoma cells （CT26 cells）. CT26 cells could induce liver to express IL-10 and TGF-β1, which may promote liver metastases of colon carcinoma.