Department of Pharmacology, Chongqing Medical University, Chongqing 400016, PR China.
Int J Oncol. 2012 Jul;41(1):292-8. doi: 10.3892/ijo.2012.1423. Epub 2012 Apr 2.
Colon cancer is one of the most common malignancies, mainly initiated by the abnormal activation of Wnt/β-catenin signaling. In this study, we investigated the proliferation inhibitory effect of berberine on colon cancer cells and the molecular basis underlying this effect. With the viability, apoptosis and cell cycle assay, we demonstrated that berberine can inhibit proliferation, induce apoptosis and cell cycle arrest in colon cancer cells. In in vivo investigation, we demonstrated that berberine can prevent the colon cancer formation initiated by dimethylhydrazine (DMH) and dextran sodium sulfate (DSS) in rats. We employed western blotting, reverse transcription and polymerase chain reaction, special antagonist, overexpression and knockdown techniques to dissect the possible molecular mechanisms mediating the function of berberine. We found that the protein levels of β-catenin in the nucleus and cytoplasm were all reduced after treating the colon cancer cells with berberine, and this may not result from accelerating the degradation of β-catenin in the cytoplasm, but from inhibiting the mRNA expression of β-catenin. Our results indicate that berberine can be a potential chemoprevention and chemotherapy agent for human colon cancer by targeting Wnt/β-catenin signaling.
结直肠癌是最常见的恶性肿瘤之一，主要由 Wnt/β-连环蛋白信号通路的异常激活引发。在本研究中，我们研究了小檗碱对结肠癌细胞的增殖抑制作用及其作用机制。通过细胞活力、凋亡和细胞周期检测，我们证实小檗碱可抑制结肠癌细胞增殖、诱导凋亡和细胞周期停滞。在体内研究中，我们证实小檗碱可预防二甲基肼（DMH）和葡聚糖硫酸钠（DSS）诱导的大鼠结直肠癌的形成。我们采用 Western blot、反转录和聚合酶链反应、特异性拮抗剂、过表达和敲低技术，解析了小檗碱发挥作用的可能分子机制。我们发现小檗碱处理结肠癌细胞后，核内和胞质内的β-连环蛋白蛋白水平均降低，这可能不是通过加速β-连环蛋白在细胞质中的降解，而是通过抑制β-连环蛋白的 mRNA 表达。我们的研究结果表明，小檗碱通过靶向 Wnt/β-连环蛋白信号通路，可能成为人类结直肠癌的一种有潜力的化学预防和化疗药物。
