氟尿嘧啶与生长抑素受体基因联合治疗鼠 胰腺癌移植瘤的研究

目的 ： 观察生长抑素二型受体(SSTR2)基因体内转染后裸鼠胰腺癌移植瘤对5-氟尿嘧啶（5-FU）的反应，并探讨其可能机制。方法 ：将人胰腺癌细胞株panc-1种植于裸鼠背部皮下形成胰腺癌移植瘤模型。成模后动物随机分成4组（每组6只）;I组为对照组;II组为腹腔注射5-FU治疗组;III组为瘤内注射pCMV-6C-SSTR2-脂质体转染SSTR2基因治疗组;IV组为基因治疗+5-FU治疗组。观察肿瘤生长速度，测量瘤体大小及重量。用免疫组织化学方法和免疫印迹技术(Westernblot)检测转染效率;用凋亡原位检测方法(Tunel)检测胰腺癌细胞的凋亡率。结果 ：体内转染后SSTR2可重新表达。5-FU和SSTR2基因联合治疗(IV)组肿瘤生长速度显著慢于单独基因治疗(III)组及单独5-FU治疗(II)组和空白对照(I)组（ P <0.01）;最终肿瘤大小，重量也显著小于其他3组（均 P <0.01），而癌细胞凋亡率显著高于其他3组（均 P <0.01）。结论 ：SSTR2重新表达后可增强胰腺癌细胞对化疗药物5-FU的敏感性，联合5-FU 和SSTR2基因治疗可望成为治疗胰腺癌新的途径。

Reexpression of somatostatin receptor type2 gene can enhance the effect of5-FU on pancreatic carcinoma in vivo

Abstract:Objective ：To observe the therapeutic effect of 5-FU on pancreatic carcinoma after xenografts transfected with SSTR2 in vivo. Methods ：Human pancreatic cancer cells (panc-1) were inoculated subcutaneously to the back of nude mice. The animals were then divided into 4 groups randomly( n =6/group) when tumor nodules grew to about 5mm×5mm seven days later. Group I served as an untreated control, group II received 5-FU via intraperitoneal injection, group III received an intratumoral injection of a combination of pCMV-6C-SSTR2 and lipofectamine 2000; Group IV recieved 5-FU via intraperitoneal injection and intratumoral injection of SSTR2. Finally, the animals were anesthetized and the tumors were excised and weighed. The result of transfection was detected by immunohistochemistry and Western-blot. A quantification of apoptosis rate was then performed using Tunel method. Results ：The expression of SSTR2 was detected in pancreatic xenografts of group III and IV transfected by pCMV-6C-SSTR2-lipofectamine2000. Combination of SSTR2 gene therapy and 5-FU chemotherapy resulted in a significant effect. The tumor group rate of group IV was slower than that of the other three groups （ P <0.01），the final size and weight of tumor was smaller than that of the other three groups（ P <0.01）, but the apoptosis rate of pancreatic cancer cells was higher than that of the other three groups （ P <0.01）. Conclusions ：Reexpression of SSTR2 can ehance the sensitivity of pancreatic carcinoma cells to 5-FU; combination SSTR2 gene therapy and 5-FU chemotherapy may be a new upproach for therapy of pancreatic carcinoma.