| Objective: In 1971, Professor Folkman proposed the view that tumor growth and metastasis depend on angiogenesis. Clinical and animal experiments have confirmed that with the absence of formation of new blood vessels, tumors would no longer be increasing when the diameter or thickness of tumors reached 1-2mm. The facts were found that tumor cells can produce not only the vascular growth factor but also be induced by a variety of anti-vascular endothelial growth factor. When the tumor vascular growth factors effect more than antiangiogenic factors, tumor growth will be increasing and tumor metastasis or recurrence will be generating. To inhibit tumor angiogenesis can prevent the tumor to grow, migrate or recur. At present, many antitumor angiogenesis drugs have been applied to clinical trail, and make all sorts of malignant tumor patient benefit from it. AngiotensinⅡ(AngⅡ) is a bio-active peptides of renin-angiotensin system (RAS), and it plays an important role in the control of cardiovascular function and the regulation of water-electrolyte balance. Clinical trials and zooperies have shown that AngⅡcan promote the tumor cells to proliferate and the tumor vessels to form. To study angiotensinⅡtype 1 receptor(AT1R)antagonist candesartan on tumor new blood vessels, is good to explore the mechanism of tumor growth, metastasis and recurrence, to discuss the treatment of malignant tumor, also, is good to study the tumor targeted drugs.Methods: Experimental animals (BALB/C male mice, 50), were randomized into 5 groups: saline group (NEC), low dose group (LCA), middle dose group (MCA), high dose group (HCA) and 5-FU group. After modeling animals , make the intervene to the five groups: NEC group were lavaged with 0.9%NS(normal temperature)at 10:00AM everyday for 8days; LCA, MCA, HCA groups were lavaged with candesartan(50mg/day/kg, 100mg/day/kg, 200mg/day/kg, normal temperature)at 10:00AM everyday for 8days while 5-FU group were intraperitoneal injected for 6 days. Before the experiment, all mice were weighted, and the twice, fourth, sixth and eighth day after the experiment, all mice were weighted before giving medicine.9 days after experiment, all mice were sacrificed and tumor tissues were obtained and weighted, then they were separated into two parts, half was put into fu Marin for doing HE after fixation and immunohistochemical staining to observe tumor tissue with AT1-positive rate and microvessel density, the other half was fixed with 4% glutaraldehyde to be observed with transmission electron microscope(TEM).Results:1NEC group: mice weight increased gradually, the middleweight in the eighth day was 20.85±1.34g,the remaining mice in each group have different degrees of decline in middleweight, they were 17.13±2.89g (HCA), 18.53±2.01g(MCA),19.44±1.60g(LCA)and15.75±2.63g(5-FU).ANOVA showed that there were significant difference between each group(P <0.05)and pointed out that mice weight declined while the dose of candesartan increased. 2 After the experiment, mice life quality was analyzed. Results showed that there were significant difference between each group(P <0.05)and pointed out that mice life quality was increased while the dose of candesartan increased. 3 After the experiment, volume of liver cancer in mice eachgroupwere:233.66±1.62mm3(NEC),144.74±1.21mm3(HCA),149.18±88.72mm3(MCA), 238.63±1.42mm3(LCA)and 69.05±41.87 mm3(5-FU), ANOVA showed that there were significant difference between each group(P <0.05)and pointed out that mice tumor volume declined while the dose of candesartan increased. 4 After the experiment, mice tumor weight of each groupwere: 0.9462±0.12g (NEC), 0.5193±0.12g(HCA),0.6009±0.15g(MCA), 0.8450±0.18g (LCA) and 0.5347±0.05g (5-FU), ANOVA showed that there were significant difference between each group(P<0.05)and pointed out that mice tumor weight declined while the dose of candesartan increased. 5 After the experiment, the average of MVD in tumor were:11.70±2.63 (NEC), 4.80±0.92 (HCA), 7.30±1.06(MCA), 7.60±0.84(LCA)and10.90±1.37 (5-FU), ANOVA showed that there were significant difference between each group(P<0.01) and pointed out that (1)MVD in tumor declined gradually while the dose of candesartan increased; (2)candesartan can prevent the tumor to grow though inhibiting the growth of blood vessels, this was different from the action mechanism of 5-FU. 6 After the experiment, the expression of AT1R was analyzed. Results showed that there were significant difference between each group(P<0.05)and pointed out that candesartan can prevent the tumor'growth though AT1R.7 After the experiment, observe the tumor cells'ultrastucture. Result showed that tumor cells in each group had different degrees of collapse, necrosis and membranolysis.Conclusion: AT1R antagonist (candesartan) can significantly inhibit the growth of mice tumor and the growth of tumor blood vessels, decline the expression of AT1R and increase the life quality of mice. Candesartan may be work though the AT1R.The study showed again that candesartan may be a new medicine to treat tumor. |
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