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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。
Objective: To observe the effect of 5FU sustained-release intratumoral injection on pancreatic cancer cells in nude mice and to explore its mechanism. Methods: Pancreatic cancer cell line PC3 was cultured in vitro and 70 nude mice were inoculated with 2 × 106 cells respectively. After 4 weeks, 60 nude mice with the same tumor size were selected and randomly divided into 5 groups: NS group, 5FU group (10mg / kg), matrix implantation group and 5FU sustained release agent (4mg / kg) Group and 5FU sustained release (1mg / kg) group. The tumor size was measured before treatment and within 14 days after treatment. The growth rate of tumor was calculated. The histological changes and cell division index were observed. The protein expressions of bcl2 and Bax were detected by immunohistochemistry. The expression of bcl2 and Bax was detected by using deoxynucleotidyl transferase Apoptosis index (AI) was detected by nick end labeling (TUNEL). Results: The growth of nude mice transplanted with intratumoral injection of 5FU slowed down (P <0.05), and the final tumor weight was less than that of other groups (P <0.05). The cell division index was also lower than that of other groups (P < 0.05). Inflammatory reaction and intimal thickening of tumor in 5FU sustained-release intratumoral injection group were significantly higher than those in other groups (P <0.05). The expression of bcl2 protein in nude mice bearing intratumoral tumor was significantly lower than that in other groups, while the protein expression of Bax in tumor-bearing nude mice was significantly higher than that in other groups <0.05). CONCLUSION: 5FU sustained-release intratumoral injection can significantly inhibit the growth of pancreatic cancer in nude mice, and its mechanism is related to the inflammatory reaction and intimal thickening caused by drugs in the tumor tissue, which may be related to the induction of tumor cells Related to apoptosis.