The Influence Of The Biological Behaviour And Mechanism Of Bladder Cancer By Angiotensin â…¡ Type 1 Receptor Inhibitor Valsartan

Objective:To investigate the relationship between the expressions of AT1R,MMP2,MMP9 and the abilities of proliferation, migration and invasion in human bladder carcinoma cell lines. To study the effect of Angiotensin Ⅱ inhibitors, which is Ang Ⅱ 1 receptor inhibitor(ARB)valsartan on Ang Ⅱ —induced bladder cancer cell line ATIR, MMP2, MMP9 protein and gene expression. To find out new experimental data and potention target in the treatment of bladder cacinoma.Methods:Treating bladder cancer cell line EJ-M3, EJ,BIU-87 alone with ARB valsartan. The MTT cell proliferation was detected, Invasion and migration of three cells were examed in vivo by wound healing assay and Transwell chamber migration assay. western blot method to detect ATIR. MMP2, MMP9 protein levels, Real-Time PCR method of detection AT1R, MMP2, MMP9 gene relative expression.Results:Use the difference of density 10-2mol/L,10-3mol/L、10-4mol/L、10-5mol/L、 10-6mol/L、10-7mol/L、10-8mol/L、10-9mol/L valsartan treated cells, determined by MTT experiment to choose valsartan for 10-3mol/L as the final concentration of drug concentration in cells for the following experiments.The number of cell migration to the scratch area at 24h of EJ-M3 the control group (2.28±0.07) was much more than experimental group (1.57±0.12), (p<0.05), the number of EJ control group (1.66±0.13) was much more than the experimental group (1.07±0.04) (p<0.05), the number of BIU-87 control group (1.24±0.09) was much more than the experimental group (0.81±0.11) (p<0.05). The penetrating cell number of EJ-M3 control group (233.39±8.18) was much more than the experimental group (154.28±6.24) (p<0.01), the number of EJ control group (150.05±4.73)was much more than the experimental group (107.88±6.38)(p<0.01), the number of BIU-87 control group (87.19±5.56) was much more than the experimental group (50.81±3.41) (p<0.01), there were significantly differences among three cell lines(p<0.01).The protein of AT1R、MMP2,MMP9 was expressed in three cell lines, the relative optical density of AT1R in EJ-M3 control group (3.4871±0.3264) and experimental group(0.6991±0.1264), EJ control group(1.5198±0.1123)experimental group (0.9198±0.1223), BIU-87 control group (2.2152±0.0112) experimental group (0.5288±0.1214), the differences were significant between three cell lines(p<0.01). The relative optical density of MMP2 in EJ-M3 control group (3.0571±0.2384) and experimental group (1.4771±0.1174), EJ control group (1.4079±0.1028)experimental group (0.4579±0.1021), BIU-87 control group (2.9102±0.1302) experimental group (0.5429±0.1384), the differences were significant between three cell lines(p<0.01). The relative optical density of MMP9 in EJ-M3 control group (0.9885±0.1894) and experimental group(0.5311±0.1079), EJ control group(0.7326±0.0121)experimental group (0.2178±0.0203), BIU-87 control group (0.5112±0.0172) experimental group (0.2078±0.0229), the differences were significant between three cell lines(p<0.01).The gene of ATIR、MMP2, MMP9 was expressed in three cell lines, The absorption value of AT1R in EJ-M3 control group (8.32±0.31) and experimental group (3.39±0.14), EJ control group (6.28±0.61) experimental group (3.31±0.19), BIU-87 control group (5.52±0.22) experimental group (2.59±0.24), the differences were significant between three cell lines(p<0.01). The absorption value of MMP2 in EJ-M3 control group (8.77±0.58) and experimental group (4.91±0.23), EJ control group(6.31±0.43)experimental group(3.86±0.13),BIU-87 control group(2.37±0.02) experimental group (0.85±0.05), the differences were significant between three cell lines(p<0.01). The absorption value of MMP9 in EJ-M3 control group (3.61±0.03)and experimental group (1.18±0.11), EJ control group (2.98±0.07) experimental group (0.94±0.02), BIU-87 control group (2.59±0.24) experimental group (0.85±0.02), the differences were significant between three cell lines(p<0.01).Conclusion:Ang Ⅱ could promote bladder cancer cell line AT1R, MMP2, MMP9 protein and gene expression, which expression could be AngⅡ inhibitors valsartan inhibited, Ang Ⅱ. inhibitors may be a kind of new control of bladder cancer metastasis and prolong survival in patients with bladder cancer drug.