Inhibitory effect of angiotensin II type 1 receptor antagonist on pancreatic cancer of nude mice / 第二军医大学学报

ABSTRACT

Objective: To investigate the inhibitory effect of selective angiotensin II type 1 receptor antagonist ZD7155 on pancreatic cancer xenografts of nude mice. Methods: Sixty nude mice were given subcutaneous injections of PaTu8988s cells to establish the pancreatic cancer xenograft models; then the animal models were evenly randomized into 3 groups low-dose (10 mg · kg-1 · d-1)ZD7155, high-dose(20 mg · kg-1 · d-1)ZD7155 and normal saline groups. Ten mice in each group were sacrificed 10 d after treatment and the tumor sizes and body weights were measured. The microvessel density (MVD) was assessed by immunostaining of endothelial cells for CD31 and the cell apoptoses were observed by transmission electron microscope. Another thirty mice were treated for 30 days; the survival period of mice and toxicity of ZD7155 were observed till the 49th day of treatment. Results: Ten days after treatment, the mean tumor volumes in the control, low-dose and high-dose groups were (35.8 ± 6.7) cm3, (21.5 ± 6.1) cm3 and (10.7 ± 4.1) cm3, respectively(P<0.01); the average tumor inhibitory rates in low-dose and high-dose groups were 22.7% and 44.6%, respectively, both significantly higher than that of the control group(P<0.01). The mean numbers of capillary vessels in the control, low-dose and high-dose ZD7155 were 16.7 ± 0.9, 11.5 ± 0.5 and 6.05 ± 0.7. respectively (P<0.01). Transmission electron microscope showed a lot of typical apoptotic cells at different stages in the 2 ZD7155 treatment groups, whereas there was no apoptotic cells in the control group. The survival periods in treated groups were significantly longer than that in the control group(P<0.01), and that of the high-dose group was longer than that of the low-dose group (P<0.01). The toxicity of ZD7155 was not apparent. Conclusion: ZD7155 can inhibit the growth of pancreatic cancer in vivo through disturbing tumor angiogenesis and inducing tumor cell apoptosis; it may possibly serve as a safe and effective agent for treatment of pancreatic cancer.