人结肠癌细胞系裸小鼠淋巴结转移的观察

Establishing lymphatic metastasis with human colon carcinoma cell line in nude mice

目的建立人结肠癌细胞系裸小鼠爪垫淋巴道转移动物模型，并评价卡培他滨抗癌药物效果。方法裸小鼠爪垫皮下注射人结肠癌HCT-116细胞，在1～6周及8周取材，进行HE染色及CEA免疫组化检测，观察种植瘤的成瘤率、生长情况、淋巴结转移规律，并口服卡陪他滨抗癌药物观察其疗效。结果种植1周后成瘤率100％。肿瘤在3～4周成指数生长。3周时见第一级帼窝腹股沟淋巴结转移（2／5），到6周时100％转移，其中腹股沟淋巴结转移阳性率76．9％（10／13）；5周时见第二级髂血管旁淋巴结转移（1／5）；到8周时见第三级肾门淋巴结转移（1／5），髂血管旁淋巴结转移（3／5），但均未见肝肺远处转移。淋巴结转移发生在肿瘤指数生长之前，HE染色及CEA免疫组化染色证实淋巴结有弥漫性癌细胞转移浸润。口服化疗药物卡培他滨能有效抑制肿瘤生长及淋巴结转移。结论成功建立了人结肠癌裸小鼠爪垫淋巴道转移模型。此模型快速简便、转移集中、转移率高，且应用此模型能够评价抗癌药物卡培他滨抗癌疗效。

Objective To establish the nude mouse model of lymphatic metastasis, and evaluate the antitumor effect of capecitabine in this model. Methods The nude mouse model of lymphatic metastasis was established by injecting human colon carcinoma cell line HCT-116 into the claw pad. The lymph nodes from popliteal fossa, inguinal groove, abdominal cavity collected at 1 -6 and 8 weeks after tumor implantation were used to observe the tumor formation rate, growth and metastasis by HE staining and immunohistochemistry of CEA. Meanwhile, capecitabine was administered orally to some mice to observe its anti-tumor effect. Results The tumor formation rate was 100% 1 week after injection, and the exponential growth phase was at 3 -4 weeks. The first lymph node metastasis to groin-popliteal fossa was found at the 3th week （2/5）, and at the 6th week the metastasis rate was 100% , and the positive metastasis rate of lymph nodes at groin was 76.9% （10/13）. At the 5th week, the second lymph node metastasis to ilio-blood-vessel side was found （1/5）. The third lymph node metastasis to renal hilum was found at the 8th week （ 1/5 ）, and meanwhile the rate of lymph node metastasis to ilio-blood-vessel side was 60% （3/5）, No distant metastasis to the liver and lungs was found. Implanted tumors developed lymph node metastases before exponential growth phase. There was diffuse cancer cell metastasis in lymph nodes, which can be approved through HE staining and immunohistochemistry of CEA. Oral intake of capecitabine suppressed the volume of the implanted tumor and significantly inhibited the metastasis to lymph nodes. Conclusion The nude mouse model of lymphatic metastasis is successfully established through injecting human colon carcinoma cell line to the claw pad. The model is simple, of rapid and concentrated transfer as well as high transfer rate. In addition, this model can be used to evaluate the anti-tumor effect of capecitabine.