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目的:探讨选择性血管紧张素Ⅱ1型受体拮抗剂ZD7155对裸鼠胰腺癌的抑制作用及其作用机制。方法:60只裸鼠接种胰腺癌PaTu8988s细胞建立胰腺癌移植瘤模型,成瘤后随机分成对照组、低剂量(10 mg·kg~(-1)·d~(-1))ZD7155治疗组和高剂量(20 mg·kg~(-1)·d~(-1))ZD7155治疗组,每组20只。治疗10 d后每组各处死10只裸鼠.测量肿瘤体积.称取瘤体质量.免疫组化检测移植瘤新生血管的CD31表达,透射电镜观察细胞凋亡;其余裸鼠共治疗30 d.记录生存期并观察ZD7155的毒副作用等共49 d。结果:(1)对照组和低、高剂量治疗组的实体瘤平均体积分别为(35.8±6.7)、(21.5±6.1)、(10.7±4.1) cm~3(P<0.01)。(2)低剂量组以及高剂量组在治疗后10 d的平均抑瘤率分别为22.7%和44.6%(P<0.01).与对照组相比均具有统计学意义(P<0.01)。(3)对照组和低、高剂量组平均微血管数目分别为16.7±0.9、11.5±0.5、6.05±0.7(P<0.01)。(4)对照组细胞未见凋亡改变,两治疗组均可见大量典型的处于不同阶段的凋亡细胞。(5)治疗组裸鼠生存期较对照组显著延长(P<0.01),而且高剂量组裸鼠生存期较低剂量组亦显著延长(P>0.01)。(6)未见明显毒副作用。结论:选择性血管紧张素Ⅱ1型受体拮抗剂在体内能抑制胰腺癌细胞生长、抑制肿瘤血管生成、促进肿瘤细胞凋亡,可望成为治疗胰腺癌的安全有效药物。
Objective: To investigate the inhibitory effect of selective angiotensin Ⅱ type 1 receptor antagonist ZD7155 on pancreatic cancer in nude mice and its mechanism. METHODS: Sixty nude mice were inoculated with pancreatic cancer cell line PaTu8988s to establish a pancreatic carcinoma xenograft model. After the tumor was established, the mice were randomly divided into control group, low dose (10 mg · kg -1 · d -1) ZD7155 treatment group and High dose (20 mg · kg -1 · d -1) ZD7155 treatment group, 20 rats in each group. After 10 days of treatment, 10 nude mice were sacrificed in each group. The tumor volume was measured and the tumor mass was weighed. The expression of CD31 was detected by immunohistochemistry and the apoptosis was observed by transmission electron microscopy. Record survival and observe the side effects of ZD7155 a total of 49 d. Results: (1) The average volumes of solid tumors in the control group and the low and high dose treatment groups were (35.8 ± 6.7), (21.5 ± 6.1) and (10.7 ± 4.1) cm ~ 3, respectively (P <0.01). (2) The average tumor inhibition rates of the low-dose group and the high-dose group after 10 days of treatment were 22.7% and 44.6%, respectively (P <0.01), which were significantly lower than those in the control group (P <0.01). (3) The average number of microvessels in control group and low and high dose groups were 16.7 ± 0.9, 11.5 ± 0.5 and 6.0 ± 0.7 respectively (P <0.01). (4) There was no apoptosis in the control group. A large number of typical apoptotic cells at different stages were observed in both groups. (5) The survival time of the nude mice in the treatment group was significantly longer than that in the control group (P <0.01), and the survival time of the nude mice in the high-dose group was significantly prolonged (P <0.01). (6) No obvious side effects. Conclusion: Selective angiotensin Ⅱ type 1 receptor antagonist can inhibit the growth of pancreatic cancer cells, inhibit tumor angiogenesis and promote the apoptosis of pancreatic cancer cells in vivo, which is expected to become a safe and effective drug for the treatment of pancreatic cancer.