高转移MHCC97H细胞裸鼠原位移植瘤姑息性肝癌切除模型的建立  

Establishment of a high metastatic potential human hepatoceilular carcinoma orthotopic transplantation model with palliative liver resection in nude mice

作　　者：黄修燕[1] 黄自丽[2] 许永华[2] 黄新余[1] 周俭[3] 叶胜龙[3] 樊嘉[3] 汤钊猷[3] 郑起[1] 

机构地区：[1]上海交通大学附属第六人民医院普外科,200233 [2]上海市徐汇区中心医院影像科 [3]复旦大学肝癌研究所

出　　处：《中华肝脏病杂志》2013年第8期604-608,共5页Chinese Journal of Hepatology

基　　金：基金项目：国家自然科学基金面上项目（81272401）;上海市卫生局中医药科研基金（2010L059A）;上海市卫生局中医药科研基金（2012QJ001A）

摘　　要：目的模拟临床肝癌切除病例构建姑息性肝切除裸鼠模型，用于研究手术对残癌的影响并探索干预策略。方法采用肝左叶单瘤源接种技术，构建高转移潜能MHCC97H细胞裸鼠原位移植瘤模型，成功建模后14d行姑息性肝切除。姑息术后14d，分析肿瘤相关基因差异表达；观察35d，检测肝内、肺脏及腹腔转移；剩余裸鼠用于观察生存期。计量资料比较用f检验，生存分析用Kaplan-Meier法（LogRank检验），尸〈0．05为差异有统计学意义。结果原位移植瘤模型成功率100％，成功构建裸鼠姑息性肝切除模型，无手术相关死亡裸鼠。姑息组裸鼠肝内转移结节多于假手术组[（11．7±4．7）个对比（6．3±2．8）个，t=-2．412，P〈0．051，腹腔转移结节多于假手术组[（9．8±3．4）个对比（5．2±2．6）个，t=-2．641，P〈0．051，肺转移结节也多于假手术组[（14．3±4．7）个对比（8．7±4．7）个，t=-2．348，P〈0．051。应用生物信息学技术进一步分析发现，肿瘤转移抑制蛋白1、肿瘤坏死因子D1、Smad2、白细胞介素1D及基质金属蛋白酶7基因在姑息组残癌基因功能网络中处于核心位置。姑息组裸鼠生存期为（60．8±2．7）d，假手术组裸鼠生存期为（51．3土1．4）d，差异有统计学意义（x2=12．850，P〈0．01）。结论单瘤源姑息性肝切除模型能有效模拟临床肝切除病例，为术后残癌生物学特性的研究及干预提供一个新的平台。Objective To construct a high metastatic potential human hepatocellular carcinoma （HCC） orthotopic transplantation model with palliative liver resection in nude mice. Methods A human HCC orthotopic nude mice model was established by administering a single inoculation of the highly metastatic MHCC97H tumor tissue （size 2 mm × 2 mm× 2 mm） into the left liver lobe. At day 14 post-inoculation, a random group of the mice received palliative liver resection; the unresected mice served as controls. Changes in expression levels of 113 genes with metastasis-related functions were evaluated in the residual HCC tissues. At day 35 post-resection, a random group of the mice were sacrificed by cervical dislocation and a comprehensive metastases examination was performed. The remaining mice were used to observe life span. All statistical analyses were performed by the SPSS vl 7.0 software, and significance was defined as P 〈 0.05. Results The nude mouse model of highly metastatic HCC with palliative liver resection was successfully established. Incidences of intrahepatic and abdominal metastases were higher in the palliative resected group （vs. unresected group： 11.7 ± 4.7 vs. 6.3 ± 2.8, t = -2.412, P 〈 0.05 and 9.8 ± 3.4 vs. 5.2 ± 2.6, t = -2.641, P 〈 0.05respectively）. In addition, the palliative resected group showed significantly enhanced pulmonary metastasis （vs. unresected group： 14.3 ± 4.7 vs. 8.7 ± 4.7, t = -2.348, P 〈 0.05）. Differential gene expression levels were found for MTSS1, TGFβ1, SMAD2, IL-1β, and MMP7, and were situated in the central position of gene fimction net of residual HCC. The life-span of the palliative resected group was significantly longer than that of the unresected group （60.8 ± 2.7 vs. 51.3 ± 1.4 days,x2 = 12.850, P 〈 0.01）. Conclusion The highly metastatic human HCC nude mouse model with palliative liver resection that was successfully constructed in this study represents a useful investigational tool to assess the biological characteristics of res

关 键 词：癌 肝细胞 姑息疗法 模型 动物 肿瘤侵润 肿瘤转移 

分 类 号：R735.7[医药卫生—肿瘤]