苦参碱调控环氧化酶-2的表达及对大鼠膀胱癌抑制作用的初步研究

目的研究苦参碱(matrine)对膀胱癌形成和发展的抑制作用及其对大鼠膀胱环氧化酶-2(COX-2)表达的影响。方法采用N-丁基-N-(4-羟丁基)亚硝基胺(BBN)诱发大鼠膀胱癌,苦参碱50、100和200 mg.kg-1灌胃给药35周后,分别以病理和免疫组织化学法观察苦参碱抑制膀胱癌的作用和对膀胱组织COX-2蛋白表达的影响。结果苦参碱对BBN诱导的大鼠膀胱癌变率无影响(P>0.05),但可抑制膀胱癌的生长(P<0.05),并可抑制浸润性膀胱癌的发生率(P<0.05)。免疫组化结果显示,与BBN组比较,苦参碱各剂量组均可降低大鼠膀胱癌组织中COX-2蛋白的表达(P<0.05)。结论苦参碱对BBN诱导大鼠膀胱癌的发生无抑制作用,但对膀胱癌的生长和进展具有抑制作用,其机制与抑制大鼠膀胱组织中COX-2蛋白的表达有关。

Preliminary study on inhibitory effect of matrine on bladder cancer via regulation of cyclooxygenase-2 expression in rats

Aim To investigate the inhibitory effect of matrine on bladder tumor growth and invasion in rat given N-butyl-(-4-hydroxybutyl) nitrosamine(BBN) and its effect on protein expression of cyclooxygenase-2(COX-2).Methods Male Sprague-Dawley rats were treated with and without BBN for 8 weeks.In addition,they were also treated with and without matrine(50,100 and 200 mg·kg-1·d-1) for 35 weeks.Histopathological diagnosis and immunohistochemical method were established to evaluate the inhibitory effect of matrine on bladder tumor invasion and expression of cyclooxygenase-2 protein.Results Oral administration of matrine(50,100 and 200 mg·kg-1·d-1) incidence of cancer cells were similar with BBN group(P>0.05),however,the frequency of invasive tumors in matrine(50,100 mg·kg-1·d-1) treated rats were significantly lower(15.4%,9%) than in those given BBN alone(50%)(P<0.05).Bladder weight and protein expression of COX-2 in matrine(50,100 and 200 mg·kg-1·d-1) group were also significantly lower than in BBN rats(P<0.05).Conclusions The results shows that matrine has no anti-carcinogenic effect,but inhibits tumor growth and invasion in BBN-induced bladder cancer in rats,through the inhibition of COX-2 protein expression.