中华普通外科杂志
中華普通外科雜誌
중화보통외과잡지
CHINESE JOURNAL OF GENERAL SURGERY
2012年
2期
123-126
,共4页
刘亮%徐华祥%王文权%汤钊猷
劉亮%徐華祥%王文權%湯釗猷
류량%서화상%왕문권%탕쇠유
癌,肝细胞%肿瘤转移%缺氧%肝动脉阻断%上皮-间质转化
癌,肝細胞%腫瘤轉移%缺氧%肝動脈阻斷%上皮-間質轉化
암,간세포%종류전이%결양%간동맥조단%상피-간질전화
Carcinoma,hepatocellular%Neoplasm metastasis%Anoxia%Hepatic arterial occlusion%Epithelial mesenchymal transition
目的 探讨抑制残癌细胞上皮-间质转化对肝动脉断流后肝癌增强的转移潜能的影响.方法 采用MHCC97肝癌细胞系和52只BALB/c-nu/nu裸鼠,建立转移性人肝癌裸鼠原位移植并肝动脉结扎(hepatic artery ligation,HAL)模型.另12只荷瘤裸鼠行假手术设为对照.分别观察肝动脉结扎+阻滞剂LY294002以及肝动脉结扎+不同剂量干扰素α(intererin-α,IFN-α)对移植瘤生长和肺转移率的影响.体外将肝癌细胞MHCC97置于缺氧环境中培养.Western blot检测细胞和移植瘤内HIF-1 α、E-cadherin、N-cadherin、Twist表达.结果 肝动脉结扎虽然减小肝癌移植瘤体积(2002.97 ±331.28) mm3 vs.(3921.23 ±786.21) mm3,t =4.052,P＜0.01),但增加荷瘤裸鼠肺转移率( 10/12 vs.4/12,P＜0.05).联合阻滞剂LY294002治疗不能进一步抑制肝癌生长,但显著减少裸鼠肺转移(1/6 vs.10/12 vs.100％,P＜0.05).中等以上剂量的IFN-α(7.5×106 U/kg)显著降低肝动脉结扎诱导的肺转移率(0/6 vs.2/6 vs.100％,P＜0.01,P＜0.05).对移植瘤和细胞样本的分析证实阻滞剂LY294002或中等以上剂量的IFN-α均抑制缺氧肝癌细胞内N-cadherin和Twist上调,增加E-cadherin表达.结论 阻断肝癌细胞上皮-间质转化能够抑制缺氧诱导的肝癌侵袭、转移.
目的 探討抑製殘癌細胞上皮-間質轉化對肝動脈斷流後肝癌增彊的轉移潛能的影響.方法 採用MHCC97肝癌細胞繫和52隻BALB/c-nu/nu裸鼠,建立轉移性人肝癌裸鼠原位移植併肝動脈結扎(hepatic artery ligation,HAL)模型.另12隻荷瘤裸鼠行假手術設為對照.分彆觀察肝動脈結扎+阻滯劑LY294002以及肝動脈結扎+不同劑量榦擾素α(intererin-α,IFN-α)對移植瘤生長和肺轉移率的影響.體外將肝癌細胞MHCC97置于缺氧環境中培養.Western blot檢測細胞和移植瘤內HIF-1 α、E-cadherin、N-cadherin、Twist錶達.結果 肝動脈結扎雖然減小肝癌移植瘤體積(2002.97 ±331.28) mm3 vs.(3921.23 ±786.21) mm3,t =4.052,P＜0.01),但增加荷瘤裸鼠肺轉移率( 10/12 vs.4/12,P＜0.05).聯閤阻滯劑LY294002治療不能進一步抑製肝癌生長,但顯著減少裸鼠肺轉移(1/6 vs.10/12 vs.100％,P＜0.05).中等以上劑量的IFN-α(7.5×106 U/kg)顯著降低肝動脈結扎誘導的肺轉移率(0/6 vs.2/6 vs.100％,P＜0.01,P＜0.05).對移植瘤和細胞樣本的分析證實阻滯劑LY294002或中等以上劑量的IFN-α均抑製缺氧肝癌細胞內N-cadherin和Twist上調,增加E-cadherin錶達.結論 阻斷肝癌細胞上皮-間質轉化能夠抑製缺氧誘導的肝癌侵襲、轉移.
목적 탐토억제잔암세포상피-간질전화대간동맥단류후간암증강적전이잠능적영향.방법 채용MHCC97간암세포계화52지BALB/c-nu/nu라서,건립전이성인간암라서원위이식병간동맥결찰(hepatic artery ligation,HAL)모형.령12지하류라서행가수술설위대조.분별관찰간동맥결찰+조체제LY294002이급간동맥결찰+불동제량간우소α(intererin-α,IFN-α)대이식류생장화폐전이솔적영향.체외장간암세포MHCC97치우결양배경중배양.Western blot검측세포화이식류내HIF-1 α、E-cadherin、N-cadherin、Twist표체.결과 간동맥결찰수연감소간암이식류체적(2002.97 ±331.28) mm3 vs.(3921.23 ±786.21) mm3,t =4.052,P＜0.01),단증가하류라서폐전이솔( 10/12 vs.4/12,P＜0.05).연합조체제LY294002치료불능진일보억제간암생장,단현저감소라서폐전이(1/6 vs.10/12 vs.100％,P＜0.05).중등이상제량적IFN-α(7.5×106 U/kg)현저강저간동맥결찰유도적폐전이솔(0/6 vs.2/6 vs.100％,P＜0.01,P＜0.05).대이식류화세포양본적분석증실조체제LY294002혹중등이상제량적IFN-α균억제결양간암세포내N-cadherin화Twist상조,증가E-cadherin표체.결론 조단간암세포상피-간질전화능구억제결양유도적간암침습、전이.
Objective To investigate the effects of inhibiting epithelial mesenchymal transition (EMT) on metastastic potential of hepatocellular carcinoma (HCC) enhanced by hepatic arterial occlusion in mice. Methods Using a metastatic human HCC orthotopic nude mice model (MHCC97),the effects of hepatic artery ligation (HAL) alone,combination of HAL and phosphatidylinositol 3-kinase (PI3K)inhibitor LY294002,or combination of HAL and interferon-α (IFN-α) on the growth of planted human HCC cells and pulmonary metastasis were evaluated,respectively.The cells and tumor tissues specimens were analyzed through expression of Akt,p-Akt,E-cadhein,N-cadherin and Twist. Results HAL inhibits tumor growth (2002.97 ± 331.28 ) mm3 vs.( 3921.23 ± 786.21 ) mm3,t =4.052,P ＜ 0.01 ),while promoting pulmonary metastatsis ( 10/12 vs.4/12,P ＜ 0.05).HAL combined with LY294002 represses significantly enhanced pulmonary metastasis rate by HAL alone (0/6 vs.6/6,P ＜ 0.01 ).Moderate-dose IFN-α (7.5 × 106 U/kg) combined with HAL failed to further reduce tumor volume compared with that of HAL alone,but inhibited markedly pulmonary metastasis (2/6 vs.6/6,P ＜ 0.05 ).The augmented level of N-cadherin and Twist in tumor tissues due to HAL reduced by LY294002 or 7.5 × 106 U/kg IFN-α.The arrest of EMT by LY294002 or IFN-α in HAL-treated xenografts was further demonstrated by the in vitro response of hypoxic cells to both agents. Conclusions Inhibition of EMT in HCC cells could repress enhanced metastastic potential due to hepatic arterial occlusion.
