肝癌模型裸鼠体内化疗后残余肿瘤侵袭转移潜能变化规律及其机制的实验研究  

Changes of metastatic potential of residual hepatocellular carcinoma in nude mice after in vivo chemotherapy and the corresponding mechanisms

作　　者：熊伟[1] 汤钊猷[1] 任正刚[1] 朱小东[1] 刘亮[1] 张伟[2] 王文权[1] 

机构地区：[1]复旦大学附属中山医院复旦大学肝癌研究所,上海200032 [2]天津医科大学附属肿瘤医院肝胆外科

出　　处：《中华肿瘤杂志》2012年第11期805-809,共5页Chinese Journal of Oncology

基　　金：国家“211”工程资助项目（2007-353）

摘　　要：目的研究体内化疗后残余肝癌侵袭转移潜能的变化规律及其机制。方法用MHCC97L细胞构建人肝癌裸鼠原位移植模型，成瘤后化疗组裸鼠以10mg／kg奥沙利铂腹腔注射化疗，对照组注射0．9％生理盐水，每周1次，共3次。另将化疗组和对照组的残余肝癌组织再接种于新裸鼠肝脏内，形成化疗预处理组和生理盐水对照组，观察和检测残余肝癌在新裸鼠体内的生长和转移情况，检测体内化疔后残余肝癌分子表型的变化。结果将残癌组织再接种于新裸鼠肝脏内42d后，化疗预处理组和生理盐水对照组裸鼠的肿瘤体积分别为（2624．59±491．60）l／mm^3和（3849．72±827．09）mm^3（P〈0．001）。肺连续切片检测结果显示，化疗预处理组的肺转移率为83．3％（10／12），而生理盐水对照组的肺转移率为25．0％（3／12），差异有统计学意义（P=0．012）。免疫组化检测结果显示，化疗预处理组肿瘤组织中E-eadherin表达显著下调，N-eadherin和vimentin表达显著增强，转录因子Snail表达上调，表明化疗后残癌组织发生上皮-间质转化（EMT）。结论体内化疗后残余肝癌生长减慢，肺转移能力显著增强，残癌组织发生EMT。Objective To explore the changes of metastatic potential of residual hepatocellular carcinoma （HCC） after in vivo chemotherapy and its mechanism. Methods Nude mouse models of orthotopie HCC in the nude mouse livers was established using human hepatocellular carcinoma cell line MHCC97L cells. Oxaliplatin （10 mg/kg, once per week） was administered intraperitoneally （i. p. ） to mice in the trial group. Mice in the control group received 0.2 ml of 0.9% sodium chloride on the same days. On day 7 after the third injection, all mice were sacrificed and tumor fragments of equal volume （2 mm ×2 mm×2 mm） from each mouse of the oxaliplatin-treated and untreated groups were reinoculated into the livers of each new recipient mouse correspondingly. The growth, metastasis and molecular phenotype of the reinoculated tumors in both groups were determined. Results In the new recipient mice, compared with untreated tumors, oxaliplatin pre-treated tumors grew significantly slower [ （2624.59 ± 491.60） mm3 vs. （3849.72 ±827.09） mm3 , P 〈0.001], but gave more spontaneous metastasis to the lung （10/12 vs. 3/12, P=0. 012）. A decreased expression of E-cadherin and increased expression of N-cadherin, vimentiu and transcription factor Snail were detected in the oxaliplatin pre-treated tumors by immunohistochemistry, which provided the evidence of epithelial mesenchymal transition （EMT） in these tumors. Conclusion Residual hepatocellular carcinomas after in vivo chemotherapy grow slower but gain enhanced metastatic potential to the lung, associated with epithelial mesenchymal transition.

关 键 词：肝肿瘤 药物疗法 奥沙利铂 肿瘤侵袭 肿瘤转移 

分 类 号：R735.7[医药卫生—肿瘤]