5-氟尿嘧啶缓释剂瘤内注射治疗胰腺癌的实验研究

目的:观察5FU缓释剂瘤内注射对裸鼠胰腺癌肿瘤细胞的影响,探讨其作用机制。方法:体外培养胰腺癌细胞株PC3,以2×106个细胞分别接种于70只裸鼠。4周后挑选肿瘤大小一致的裸鼠60只,随机分成5组,即静脉NS对照组、5FU静注组(10mg/kg)、基质植入组、5FU缓释剂(4mg/kg)植入组及5FU缓释剂(1mg/kg)植入组。于治疗前及治疗后14d内测量肿瘤大小,计算肿瘤生长速度;观察组织学变化和细胞分裂指数;免疫组化法测定bcl2和Bax的蛋白表达水平;采用脱氧核苷酸末端转移酶介导的缺口末端标记法(TUNEL)检测凋亡指数(AI)。结果:5FU缓释剂瘤内注射组裸鼠移植瘤生长速度减慢(P<0.05),最终瘤重小于其他各组(P<0.05);细胞分裂指数亦均低于其他各组(P<0.05)。5FU缓释剂瘤内注射组肿瘤组织中炎症反应和血管内膜增厚程度明显高于其他各组(P<0.05)。5FU缓释剂瘤内注射组荷瘤裸鼠的bcl2基因蛋白表达明显低于其他各组,而Bax基因的蛋白表达明显高于其他各组,其肿瘤细胞的AI明显高于其他各组(P<0.05)。结论:5FU缓释剂瘤内注射可明显抑制裸鼠胰腺癌瘤体的生长,其作用机制与药物在肿瘤组织中引起的炎症反应和血管内膜增厚等因素有关,并可能与诱导肿瘤细胞的凋亡有关。

Experimental study on intra-tumor injection of slow-released 5-FU in the treatment of pancreatic carcinoma

Objective To study the effect of intra,tumor injection of slow,released 5,FU on pancreatic carcinoma; and to explore its mechanism of action. Methods Human pancreatic carcinoma strain PC,3 cells were cultured and ino,culated subcutaneously under the armpits of 70 Athymic mice. Sixty mice with similar tumor size were chosen 4 weeks afer inoculation. They were divided into 5 groups according to various modes of treatments given: NS intravenous injection as the control group, 5,FU (10 mg/kg) intravenous injection group, basic medium injection group, intra,tumor injection of slow,released 5,FU (4 mg/kg) group and intra,tumor injection of slow,released 5,FU (1 mg/kg) group. Tumor size was measured before treatment and 14 days after treatment. Tumors were excised. Tumor cell cycle kinetics was analyzed by microscopy. The apoptotic index (AI) was detected by terminal,deoxynucleotide transferase mediated d,UTP nick end labeling (TUNEL) and expression of bcl,2 and Bax by immunohistochemistry. Results The growth rate was lower in the 2 intra,tumor injection of slow,released 5,FU groups (treatment groups) than in other groups (P<0.05). The Mitotic Index were lower in the 2 treatment groups than in the other groups (P<0.05). The extent of local inflammation and increase in thickness of blood vessel endothelium were more evident in the treatment groups than in the other groups (P<0.05). AI was significantly higher in the treatment groups than in the other groups (P<0.05). The expression of bcl,2 was markedly decreased but that of Bax markedly increased in the treatment groups than in the other groups (P<0.05). Conclusions Intra,tumor injection of slow,released 5,FU can inhibit the growth of pancreatic carcinoma by inducing local inflammation and thickening of blood vessel endothelium, and up,regulating apoptosis of the pancreatic cancer cells.