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目的:观察小檗碱对实验性结肠癌的防治作用及其与环氧酶-2表达的关系。方法:以二甲肼(1-2 dimethyl-hydrazine,DMH)40 mg.kg-1皮下注射+1%葡聚糖硫酸钠(dextran sodium sulfate,DSS)水溶液饮用诱导形成大鼠结肠癌模型。观察小檗碱(100 mg.kg-1.d-1,1周5 d)和美洛昔康(1.35 mg.kg-1.d-1,1周5天)灌服,连续16周对大鼠体重、异常隐窝灶(abrrant crypt foci,ACF)和结肠癌发生率的影响。采用四甲基谷氮蓝法(MTT)研究小檗碱和美洛昔康抑制培养的人结肠癌lovo细胞增殖的量-效和时-效关系;用RT-PCR和Western blot法检测各组细胞COX-2 mRNA和蛋白表达水平。结果:与模型组相比,小檗碱明显改善DMH+DSS诱癌过程中大鼠的恶液质状态并阻遏体重减轻,显著减少实验第10周大鼠结肠ACF数和明显降低结肠癌的发生率;其作用与美洛昔康组相似。小檗碱呈浓度和时间依赖性明显抑制lovo细胞增殖,其作用6,12,24 h的IC50均显著小于美洛昔康。小檗碱也呈浓度依赖性降低lovo细胞中COX-2 mNRA和蛋白表达。结论:小檗碱能抑制DMH和DSS联合使用诱导大鼠早期ACF的形成和结肠癌发生,其作用途径可能至少与细胞抑制COX-2表达有关。
Objective: To observe the preventive and therapeutic effects of berberine on experimental colon cancer and its relationship with the expression of cyclooxygenase-2. Methods: Colon cancer in rats was induced by subcutaneous injection of dextran sodium sulfate (DSS) solution with 40 mg · kg-1 dimethylhydrazine (DMH) 40 mg · kg-1. Berberine (100 mg.kg-1.d-1, week 1, week 5) and meloxicam (1.35 mg.kg-1.d-1, week 1 and 5) were administered orally for 16 weeks Rat body weight, abrrant crypt foci (ACF) and the incidence of colon cancer. The MTT method was used to study the dose-response and time-response relationship of berberine and meloxicam in inhibiting the proliferation of human colon carcinoma lovo cells. RT-PCR and Western blot were used to detect the cell proliferation COX-2 mRNA and protein expression levels. Results: Compared with the model group, berberine significantly improved the state of cortisol and repressed the body weight of rats induced by DMH + DSS, significantly reduced the number of colon ACF and significantly decreased the incidence of colon cancer in the 10th week Rate; its role and meloxicam group similar. Berberine inhibited the proliferation of lovo cells in a concentration-and time-dependent manner, and the IC50 values at 6, 12 and 24 h were significantly lower than those of meloxicam. Berberine also reduced COX-2 mNRA and protein expression in lovo cells in a concentration-dependent manner. CONCLUSION: Berberine can inhibit the combination of DMH and DSS in inducing early ACF formation and colon carcinogenesis in rats, and its mechanism of action may at least be related to the inhibition of COX-2 expression by cells.