Effect Of ATRA Combined With Interferon Alpha-2a On The Animal Model Of Bladder Tumor

Purpose: To observe the effect of all trans retinoic acid (ATRA) combined with Interferon α -2a on the Wistar rats model of bladder tumor and discuss the mechanism of the therapeusis.Methods: 50 female Wistar rats, 6-7 weeks old, which were separated into 4 groups randomly, were irrigated 0.1mL 20mg/ml N-methyl-N-nitrosourea (MNU) into their bladders every other week (0, 2^nd, 4^th and 6^th week) for a total of four doses to induce the bladder tumor. They were treated by way of irrigation of bladder with either 0.2ml dimethyl sulfoxide (DMSO), 300 thousand IU interferon-alphα-2a (IFN-α-2a), 3mg ATRA, and 3mg ATRA combined with 300 thousand IU IFN-α-2a respectively every week (9 ^th, 10 ^th, 11 ^th and 12^th week) for a total of four times. In the thireenth week, all rats were weighted before they were killed, subsequetly their bladders were weighted and harvested for observation by naked eye and microscope. Their bladder tumuor was harvested for examination by flow cytometry (FCM), in which we can analyze their apoptosis and cell cycle.Results: The weight of bladders in ATRA+ IFN-α-2a group was (0.19 ± 0.05 g) lower than those in DMSO group (0.46 ± 0.09 g), IFN-α-2a group(0.31±0.11 g) and ATRA group(0.28 ± 0.07) (P<0.05). The stages and grades of bladder tumor in ATRA+ IFN-α-2a group were statistically descended compared with those in DMSO group (P<0.05). The apoptosis rate of bladder tumor in ATRA+ IFN-α-2a group (13.43 ± 3.06%) was higher than those in DMSO group (3.15 ± 1.13%), IFN-α-2a group (4.14±1.26%) and ATRA group (8.46 ± 2.04%) (P<0.05). The proliferation index in ATRA+ IFN-α-2a group (19.95±4.17%) was lower than those in ATRA group (49.24±6.54%), IFN-α-2a group (40.10 ± 5.06%) and ATRA group(28.49±3.40%) (P<0.05).Conclusion: 1. The irrigation of bladder with ATRA+ IFN-α-2a can reduce the stages and grades of Wistar rats' bladder tumor. 2. The irrigation of bladder with ATRA has some effect in the treatment of bladder tumor; while the effect of the irrigation of bladder with IFN-α-2a was not well.3.The growth inhibition and apoptosis of ATRA ,which is enhanced by IFN-α-2a, is maybe the mechanism of ATRA combined with interferon alphα-2a in the treatment of bladder tumor .