TACE不完全栓塞对兔VX2肝癌生长及Notch2通路的影响

The effect of TACE incomplete embolization on growth and Notch2 pathway of VX2 hepatoma in rabbits

目的研究经肝动脉化疗栓塞术(TACE)不完全栓塞对兔VX2肝癌生长及Notch2通路的影响。方法用穿刺种植法建立兔VX2肝癌模型(n=16),采用随机数表法分为TACE不完全栓塞组即实验组(n=8)和对照组(n=8);分别于瘤块植入后7 d、14 d(即TACE不完全栓塞术当天)及21 d超声筛查2组肿瘤并监测肿瘤体积变化;实验组数字减影血管造影(DSA)下经肝左动脉注入碘油乳剂0.5 mL,生理盐水0.5 mL冲洗导管,建立VX2肝癌TACE不完全栓塞模型,对照组经肝左动脉注入生理盐水1 mL;CT平扫+增强检测2组TACE手术前后肿瘤形态;HE染色观察2组肿瘤细胞形态;Western blot检测2组肿瘤Notch2、缺氧诱导因子(HIF)-1α及血管内皮生长因子(VEGF)蛋白表达水平。结果16只实验兔均成功建立VX2肝癌模型;实验组DSA下均成功建立VX2肝癌不完全栓塞模型;超声测得实验组TACE不完全栓塞术后7 d肿瘤体积明显小于对照组[(2.42±0.97)cm^3 vs(.6.79±4.76)cm^3,P<0.05]。TACE手术前后CT平扫+增强证明2组肿瘤均符合肝癌或肝癌TACE不完全栓塞术后表现。对照组肿瘤HE染色见大量肝癌细胞,实验组肝癌细胞大片坏死并周边残存少量肝癌细胞。实验组肝癌组织HIF-1α蛋白表达水平明显高于对照组(P<0.05),2组间Notch2及VEGF蛋白表达差异无统计学意义。结论TACE不完全栓塞对兔VX2肝癌生长有抑制作用,并且可以形成肿瘤缺氧微环境,诱导HIF-1α高表达。

Objective To study the effect of incomplete embolization of hepatic artery chemoembolization(TACE)on the growth of VX2 liver cancer and Notch2 pathway in rabbits.Methods The puncture and implantation method was used to establish rabbit VX2 liver cancer model(n=16).The model rabbits were divided into TACE incomplete embolization group(experimental group,n=8)and the control group(n=8)by random number table.Ultrasound was used to screen the tumor and changes of tumor volume on the day 7,day 14(on the day of TACE incomplete embolization)and day 21 after tumor implantation.In the experimental group,the model of TACE incomplete embolization of VX2 hepatoma was established under DSA(0.5 mL lipiodol emulsion and 0.5 mL normal saline were injected into the left hepatic artery).In the control group,1 mL normal saline was injected into the left hepatic artery.The tumor morphology was detected by ordinary CT scan and enhanced CT scan.HE staining was used to observe the morphology of tumor cells.Western blot assay was used to detect the expressions of Notch2,HIF-1αand VEGF proteins.Results The VX2 hepatoma model was successfully established in 16 rabbits.Rabbits of the experimental group were successfully established VX2 hepatoma TACE incomplete embolism model under DSA.The tumor volume(2.42±0.97)cm3 was significantly lower in the experimental group than that in the control group(6.79 cm3±4.76 cm3,P<0.05).Ordinary CT scan and enhanced CT scan before and after TACE showed that the tumors in the two groups were consistent with the performance of hepatoma or hepatoma after TACE incomplete embolization.In the control group,a large number of hepatoma cells were seen by HE staining,while in the experimental group,hepatoma cells were necrosis and a small number of hepatoma cells remained around.The expression level of HIF-1αprotein was significantly higher in the experimental group than that in the control group(P<0.05).There was no significant difference in the expressions of Notch2 and VEGF proteins between the two groups.Conclusion TACE incomplete embolization can inhibit the growth of VX2 hepatoma in rabbits and induce the high expression of HIF-1αprotein in tumor hypoxia microenvironment.