Effect Of Matrine On Urinary Bladder Cancer Induced By N-butyl-N-(4-Hydroxybutyl) Nitrosamine In Rats

Aim This study investigated the effect of matrine on urinary bladder cancer induced byN-butyl-N-（4-hydroxybutyl） nitrosamine （BBN） in rats and its effect on protein expression ofepidermal growth factor receptor.Methods Male Sprague-Dawley（SD） rats were randomly divided into control group,BBN group, the celecoxib (500mg·kg^-1·d-1) group, and different dose of matrine (50,100and200mg·kg^-1·d-1) treatment groups. To induce the bladder cancer in the SD rats, BBN wasadministrated at200mg·0.5ml^-1per rat by intragastric, twice a week for eight weeks, andsolvent control solution was given to the control rats. Matrine and celecoxib were orallyadministrated one week before BBN administration. All surviving rats were sacrificed at theend of35weeks. Histopathological and immunohistochemical method were used to evaluatethe effect of matrine on bladder tumor invasion and expression of epidermal growth factorreceptor.Results The urine pH in BBN group reduced apparently compared with controlgroup（P <0.05）,but the ion concentration corrected by creatinine changed insignificantlycompared with control group and BBN group（P>0.05）.Compared with control group, thecardiac index,lung index and spleen index were not change significantly in celecoxib groupand matrine groups（P>0.05）,however,the liver index and the kidney index was enlargedobviously （P <0.05, P <0.01）. And meantime the liver index and kidney index in matrinegroups were greater than BBN group （P <0.05, P <0.01）.The bladder weight was about140mg in control group never exceed200mg, however other groups increased significantly andthe prencentage of transcended200mg decreased significiantly in matrine groups vs BBN group（P <0.05, P <0.01）.The cancer incidence rates were70%,25%,68.4%,57.9%,37.5%in BBN group,celecoxib group and matrine treatment groups (50,100and200mg·kg^-1), respectively. Oraladministration of matrine (50,100and200mg·kg^-1·d-1) incidence of cancer cells were similarwith BBN group （P>0.05）, however, the frequency of invasive tumors in matrine (50,100mg·kg^-1·d-1) treated rats were significantly lower （15.4%,9%） than in those given BBN alone（50%）（P <0.05）.The expression index of EGFR were （0.79±0.673）,（3.845±0.972）,（2.466±0.88）,（2.691±1.045）,（2.23±0.748） and （2.739±0.814）, respectively.Protein expression of EGFR inmatrine (50,100and200mg·kg^-1·d-1) group were significantly lower than in BBN rat （P<0.05）.Conclusions The results showed that matrine had no anti-carcinogenic effect, butinhibited tumor growth and invasion in BBN-induced bladder cancer in rats, through theinhibition of EGFR protein expression.