围介入期应用奥曲肽治疗大鼠肝内移植瘤的疗效

The Therapeutic Effects of Octreotide on Transplanted Tumor of Rat′s Liver Peri-hepatic Arterial Occlusion

目的 观察围介入期应用奥曲肽治疗大鼠肝内移植瘤的效果,并初步探讨其机制。方法 采用大鼠肝内移植Walker2 5 6肿瘤模型,以肝动脉结扎(hepaticarteryligation ,HAL)的方法阻断肝动脉血供,模拟肝动脉介入栓塞。分为对照组、HAL组、HAL +奥曲肽治疗组。观察肿瘤生长抑制率、检测肿瘤组织血供、瘤组织VEGFmRNA表达水平、血清VEGF水平、肿瘤组织中生长抑素受体(somatostatinreceptor,SSTR) 1- 5mRNA表达水平并检测肿瘤组织细胞凋亡水平。结果 对照组、HAL组、HAL +奥曲肽组肿瘤体积分别为(0 .10 3±0 .0 4 3)cm3 、(0 .0 30±0 .0 18)cm3 、(0 .0 16±0 .0 0 5 )cm3 ,后2组肿瘤体积明显小于对照组(P <0 .0 1) ,肿瘤抑制率分别为70 .8%、84 .5 %。HAL +奥曲肽组肿瘤体积明显小于HAL组(P <0 .0 5 )。对照组、HAL组、HAL +奥曲肽组Hoechst33342标记细胞数分别为36 9.7±30 .2、344 .1±2 6 .0、32 3.2±4 0 .4 ,HAL +奥曲肽组标记细胞数明显少于对照组,提示其血供明显减少。HAL +奥曲肽组瘤组织VEGFmRNA表达较HAL组稍下降(P >0 .0 5 )。肿瘤组织中SSTR2 、SSTR3 表达阳性,各组之间表达无统计学显著性差异(P >0 .0 5 )。对照组、HAL组、HAL +奥曲肽组细胞凋亡率依次增高,其中HAL组、HAL +奥曲肽组分别与对照?

Purpose To observe the therapeutic effect o f octreotide on transplanted tumor in rat's liver peri-hepatic arterial occlusi on and to explore its mechanisms. Methods Walker 256 carcinosarcoma was transplanted into rat's liver to create liver cancer model.Hepatic arterial ligation (HAL) was us ed to block the hepatic arterial blood supply.Rats bearing tumor were divided in to 3 groups:control group,HAL group,and HAL plus octreotide group.Change of tumo r volume and tumor growth inhibiting rate,blood perfusion of tumor,expression of VEGF mRNA in tumor tissue,serum VEGF level,SSTR1-5 mRNA expression and tumor c ells apoptosis were evaluated. Results The mean tumor volume in control group,HAL grou p,and HAL plus octreotide group was (0.103±0.043) cm3,(0.030±0.018) cm3,an d (0.016±0.005) cm3,respectively.The tumor volume in the two behind groups wa s smaller than that in the control group (P< 0.01),and the tumor growth i nhib iting rate was 70.8% and 84.5%,respectively.Compared with the HAL group,the tumo r volume in HAL plus octreotide group decreased significantly (P<0.05).Hoech st 33342 labeled cells' number in control group,HAL group,and HAL plus octreotid e group was 369.7±30.2, 344.1±26.0,and 323.2±40.4,respectively.The number in H AL combined with octreotide group decreased significantly compared with that in control group (P<0.05),which suggested that the blood perfusion of tumor in HAL plus octreotide group decreased significantly.The expression of VEGF mRNA de creased slightly,but not significantly in HAL plus octreotide group compared wit h that in HAL group (P>0.05).SSTR-2 and SSTR-3 were detected in the tumor tissue,no significantly difference of mRNA expression level was found between groups (P>0.05).The apoptosis index of tumor cells increased in order betwee n control group,HLA group and HLA plus octreotide group.Apoptosis index of HLA g roup and HLA plus octreotide group was significantly higher than that of control group,respectively (both P<0.05). Conclusions Octreotide can promote the effects of hepat ic arterial occlusion therapy for transplanted cancer in rat's liver.Decreasing the blood perfusion of tumor after hepatic arterial blockage and inducing tumor cells apoptosis by acting on SSTR-2 and SSTR-3 may be some of its major mechan isms.