选择性COX-2抑制剂对大鼠实验性肝癌早期干预的研究

Early interference treatment with selective COX-2 inhibitor for experimental hepatocarcinoma in rats

目的:观察环氧化酶2(cyclooxygenase-2,COX-2)抑制剂对大鼠肝癌的发生及肿瘤血管生成的早期干预效果及作用机制。方法:将实验大鼠分为两组:单纯诱导组(12只)和药物干预组(40只),均给予二乙基亚硝胺(diethylnitrosamine,DEN)诱发大鼠实验性肝癌,药物干预组同时给选择性COX-2抑制剂罗非昔布(Rofecoxib)进行治疗,于第6周和第9周分批处死实验大鼠,观察病理变化;采用免疫组化法检测肝脏COX-2、肿瘤微血管密度(MVD)、抗凋亡基因Bcl-2和增殖细胞核抗原(proliferating cell nuclear an-tigen,PCNA)情况。结果:病理切片显示药物干预组大鼠肝脏的病变程度较单纯诱导组减轻;COX-2、Bcl-2在第6周及第9周、PCNA在第9周的表达干预组均低于诱导组(分别为P<0.01,P<0.05;P<0.05,P<0.01和P<0.05);MVD值两组间差异无统计学意义(P>0.05)。结论:COX-2抑制剂干扰和减缓了大鼠实验性肝癌的进程,其作用机制可能主要是通过诱导细胞凋亡及抑制细胞增殖而实现,对于肿瘤血管生成的抑制作用在诱癌早期未能显示。

Objective： To observe the effect of interference treatment and mechanism in early stage with selective COX-2 inhibitor for experimental hepatocarcinoma and angiogenises in rats. Methods： The rats were divided into two groups： inducing group （n = 12） and interferential group （n = 40）. The rats in inducing group only drank 0.01% diethylnitrosamine （DEN） water, whereas the rats in interferential group not only drank DEN water but also received selective COX-2 inhibitor Rofecoxib 30 mg/kg daily. The rats were killed in batches at the 6th and the 9th week of the experiment separately. Meanwhile, the cyclooxygenase-2（COX-2）, microvessel density（MVD）, Bcl-2 and proliferating cell nuclear antigen （PCNA） of the livers were detected by immunohistochemistry. Results： The grade of pathological change in interferential group was lighter than that in inducing group. The expressions of COX- 2 and Bcl-2 at the 6th and the 9th, PCNA at the 9th week of the experiment in interferential group was far lower than those in inducing group （ P 〈 0.01, P 〈 0.05; P 〈 0.05, P 〈 0.01 and P 〈 0.05 separately） whereas the value of MVD in two groups was low and the difference was not significant at the experiment group（ P 〉 0.05）. Conclusion： The experiment showed that the selective COX-2 inhibitor intervened and slowed the process of rat experimental liver cancer. The interferential effect in the early carcinogenesis mainly based on the suppression of tumor growth and induction of apoptosis by inhibiting COX-2 expression, and the effect on tumor angiogenesis in early carcinogenesis has not been shown .