奥曲肽增强肝动脉闭塞在治疗大鼠肝肿瘤模型中的效果。

Guo Wei-Jian, Zhuang Jun-Yan, Bai Yong-Rui, Li Jie, Cheng Yu Fan, Shen Zheng, Li Wen-Hua, Zhang Wen Zhu, Cai Rong

Oncology Department of Cancer Center, Xinhua Hospital of Shanghai Second Medical University, Shanghai, China, 200092.

Hepatogastroenterology. 2003 Mar-Apr;50(50):349-53.

BACKGROUND/AIMS: To observe if octreotide can augment the effects of hepatic arterial occlusion for transplanted cancer in rat's liver.

METHODOLOGY

Walker 256 carcinosarcoma was transplanted into rat's liver to create the liver cancer model. Hepatic arterial ligation was used to block the hepatic arterial blood supply. Rats bearing tumor were divided into three groups: control group, HAL (hepatic arterial ligation) group, and HAL plus octreotide group. Change of tumor volume and tumor growth inhibiting rate after therapy were evaluated. Hoechst 33342 labeling assay was used to analyze the blood perfusion of tumor (the labeled cells' number presenting blood perfusion). Expression of vascular endothelial growth factor and matrix metalloproteinase-1 mRNA was detected by in situ hybridization, and the level of serum vascular endothelial growth factor was assayed by ELISA.

RESULTS

Six days after hepatic arterial ligation, the mean tumor volume in control group, HAL group, and HAL plus octreotide group was 0.103 +/- 0.043 cm3, 0.030 +/- 0.018 cm3, and 0.016 +/- 0.005 cm3, respectively. The tumor volume in the two behind groups was smaller than that in the control group (P < 0.01), and the tumor growth-inhibiting rate was 70.8%, and 84.5%, respectively. Compared with the HAL group, the tumor volume in HAL plus octreotide group decreased significantly (P < 0.05). Hoechst 33342 labeled cells' number in control group, HAL group, and HAL plus octreotide group was 369.7 +/- 30.2, 344.1 +/- 26.0, and 323.2 +/- 40.4, respectively. The number in HAL 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 vascular endothelial growth factor and matrix metalloprotenase-1 mRNA decreased slightly, but not significantly in HAL plus octreotide group compared with that in HAL group (P > 0.05).

CONCLUSIONS

The results suggest that octreotide can promote the effects of hepatic arterial occlusion therapy for transplanted cancer in rat's liver. Decreasing the blood perfusion of tumor after hepatic arterial blockage maybe one of its major mechanisms.

背景/目的：观察奥曲肽是否能增强肝动脉阻断对大鼠移植性肝癌的治疗效果。

方法

将Walker 256癌肉瘤移植到大鼠肝脏建立肝癌模型。采用肝动脉结扎术阻断肝动脉血供。荷瘤大鼠分为三组：对照组、肝动脉结扎（HAL）组和肝动脉结扎加奥曲肽组。评估治疗后肿瘤体积变化及肿瘤生长抑制率。采用Hoechst 33342标记法分析肿瘤血灌注情况（标记细胞数代表血灌注）。通过原位杂交检测血管内皮生长因子和基质金属蛋白酶-1 mRNA的表达，采用ELISA法检测血清血管内皮生长因子水平。

结果

肝动脉结扎6天后，对照组、HAL组和肝动脉结扎加奥曲肽组的平均肿瘤体积分别为0.103±0.043 cm³、0.030±0.018 cm³和0.016±0.005 cm³。后两组的肿瘤体积均小于对照组（P<0.01），肿瘤生长抑制率分别为70.8%和84.5%。与HAL组相比，肝动脉结扎加奥曲肽组的肿瘤体积明显减小（P<0.05）。对照组、HAL组和肝动脉结扎加奥曲肽组的Hoechst 33342标记细胞数分别为369.7±30.2、344.1±26.0和323.2±40.4。肝动脉结扎加奥曲肽组的标记细胞数与对照组相比明显减少（P<0.05），提示肝动脉结扎加奥曲肽组肿瘤血灌注明显降低。与HAL组相比，肝动脉结扎加奥曲肽组血管内皮生长因子和基质金属蛋白酶-1 mRNA的表达略有下降，但差异无统计学意义（P>0.05）。