Department of General Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Phytother Res. 2014 Sep;28(9):1342-8. doi: 10.1002/ptr.5135. Epub 2014 Mar 4.
The therapeutic potential of baicalein against hepatoma cells was evaluated in vitro and in vivo. In cell viability assays, baicalein showed significant cytotoxicity against the hepatocellular carcinoma cell lines H22, Bel-7404, and Hep G2 and moderate cytotoxicity against immortalized human hepatocytes. Baicalein induced G0/G1-phase arrest in hepatocellular carcinoma cells, inhibited AKT, and promoted the degradation of β-catenin and cyclin D1 without activation of GSK-3β. Furthermore, baicalein significantly inhibited H22 xenograft tumor growth without causing obvious adverse effects on weight or liver and spleen weight indexes in ICR mice. Immunohistochemical analysis showed that the inhibition of tumor growth in baicalein-treated mice was associated with decreased AKT, β-catenin, and cyclin D1 expression ex vivo. Our data indicate that baicalein might regulate cyclin D1 transcription via a β-catenin-dependent mechanism, leading to cell cycle arrest at G0/G1 phase and impaired cancer cell proliferation. These results suggest that baicalein is a potential candidate for the treatment of hepatocellular carcinoma.
黄芩素对肝癌细胞的治疗潜力在体外和体内进行了评估。在细胞活力测定中，黄芩素对肝癌细胞系 H22、Bel-7404 和 Hep G2 表现出显著的细胞毒性，对永生化人肝细胞表现出中等的细胞毒性。黄芩素诱导肝癌细胞 G0/G1 期阻滞，抑制 AKT，并促进 β-连环蛋白和细胞周期蛋白 D1 的降解，而不会激活 GSK-3β。此外，黄芩素显著抑制 H22 异种移植肿瘤生长，而在 ICR 小鼠中体重或肝脾重量指数无明显不良反应。免疫组织化学分析表明，黄芩素处理小鼠肿瘤生长的抑制与 AKT、β-连环蛋白和细胞周期蛋白 D1 的表达降低有关。我们的数据表明，黄芩素可能通过 β-连环蛋白依赖性机制调节细胞周期蛋白 D1 的转录，导致 G0/G1 期细胞周期阻滞和癌细胞增殖受损。这些结果表明，黄芩素可能是治疗肝癌的潜在候选药物。
