摘要目的 研究肝动脉断流对原发性肝癌(简称肝癌)侵袭转移潜能的影响.方法 采用24只 BALB/c-nu/nu裸鼠,建立转移性人肝癌裸鼠原位移植模型.种瘤术后2周荷瘤裸鼠随机分为2组干预:一组行肝动脉结扎(hepatic artery ligation,HAL);另一组假手术作为对照.每组随机抽取6只裸鼠于干预术后4周进行肿瘤大小和肺转移率的比较,并用免疫组化(S-P法)及Western blot检测移植瘤上皮-间质转化(epithelial-mesenchymal transition,EMT)相关分子的表达;其余荷瘤动物观察生存时间.体外以100 μmol/L CoCl2模拟乏氧环境,观察MHCC97L肝癌细胞生长和凋亡以及运动和侵袭能力,用免疫荧光和Western blot检测细胞EMT标志分子的变化.结果 HAL抑制肝癌生长[(1996.8±223.6)mm3比(4049.1±596.5)mm3,P＜0.01],但增加肺转移率(6/6比1/6,P＜0.05),因此不能改善荷瘤动物生存期[(56.0±4.6)d比(60.7±5.8)d,P＞0.05].这与乏氧环境中癌细胞运动[(472.7±84.3)μm比(378.8±73.7)μm,P＜0.05]和侵袭能力[(154.4±30.5)个比(45.2±7.6)个,P＜0.01]增强有关,主要涉及E-cadherin下降及N-cadherin和Twist上调的EMT机制.结论 HAL抑制肝癌生长,促进其侵袭转移潜能,与乏氧环境中癌细胞EMT相关.

abstractsObjective To investigate the effects of the hepatic arterial occlusion on metastatic potential of hepatocellular carcinoma(HCC)in nude mice and explore its molecular background.Methods Using a metastatic human HCC orthotopic nude mice model,the effects of hepatic artery ligation(HAL)on tumor growth,metastasis and life-span were evaluated.To clarify the molecular background,the cell signalling related to migration and invasion was investigated through expression of E-cadhein,N-cadherin and Twist.The relationship between metastatic potential of cells in respose to hypoxia induced by 100 μmol/L CoCl2 and"epithelial-mesenchymal transition(EMT)"was also examined in vitro.Results HAL inhibited tumor growth(1996.8±223.6 mm~3 vs.4049.1±596.5 mm~3,P＜0.01),but promoted pulmonary metastasis(6/6 vs.1/6,P＜0.05),and did not confer any survival benefit(56.0±4.6 days vs.60.7±5.8 days,P＞0.05).The N-cadherin and Twist were increased in tumors after HAL.In vitro : The proliferation of MHCC97L cells arrest under hypoxic conditions acompanied with increased invasion(472.7±4.3 μm vs.378.8±73.7 μm,P＜0.05)and migration(154.4 ± 30.5 vs.45.2 ± 7.6,P＜0.01),which was related to the changes associated with EMT.Conclusion In nude mice model,HAL does not prolong life span although temporary inhibits liver tumor growth but enhances metastatic potential by activation of EMT pathways.