Department of Traditional Chinese Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China.
BMC Complement Altern Med. 2013 Jul 19;13:185. doi: 10.1186/1472-6882-13-185.
Hepatocellular carcinoma (HCC) is a common and aggressive cancer, and the treatment options are limited for patients with advanced HCC. Bufalin, the major digoxin-like component of the traditional Chinese medicine Chansu, exhibits significant anti-tumor activities in many tumor cell lines. In the present study, we investigated the effect of bufalin on the inhibition of an AKT-related signaling pathway, and examined the relationship between regulatory proteins and anti-tumor effects in hepatoma cells.
Proliferation, wound healing, transwell-migration/invasion and adhesion assays were performed in HCCLM3 and HepG2 cell lines. The protein levels of pAKT, AKT, pGSK3β, GSK3β, pβ-catenin, β-catenin, E-cadherin, MMP-9, and MMP-2 were measured by western blot analysis. E-Cadherin and β-catenin expression levels were also evaluated by immunofluorescence.
Bufalin inhibited hepatoma cell proliferation, migration, invasion and adhesion. In addition, treatment with bufalin significantly decreased the levels of pAKT, pGSK3β, MMP-9, and MMP-2, while increasing the levels of GSK3β and E-cadherin and suppressing the nuclear translocation of β-catenin.
Bufalin is a potential anti-HCC therapeutic candidate through its inhibition of the AKT/GSK3β/β-catenin/E-cadherin signaling pathway. Further studies with bufalin are warranted in patients with HCC, especially those with the disease at advanced stages.
肝细胞癌（HCC）是一种常见且侵袭性强的癌症，晚期 HCC 患者的治疗选择有限。蟾酥是一种传统中药，其主要的洋地黄样成分蟾毒配基在许多肿瘤细胞系中表现出显著的抗肿瘤活性。在本研究中，我们研究了蟾毒配基对 AKT 相关信号通路抑制的影响，并研究了调节蛋白与肝癌细胞抗肿瘤作用之间的关系。
在 HCCLM3 和 HepG2 细胞系中进行增殖、划痕愈合、Transwell 迁移/侵袭和黏附测定。通过 Western blot 分析测定 pAKT、AKT、pGSK3β、GSK3β、pβ-catenin、β-catenin、E-cadherin、MMP-9 和 MMP-2 的蛋白水平。通过免疫荧光法评估 E-cadherin 和 β-catenin 的表达水平。
蟾毒配基抑制肝癌细胞增殖、迁移、侵袭和黏附。此外，蟾毒配基处理显著降低了 pAKT、pGSK3β、MMP-9 和 MMP-2 的水平，同时增加了 GSK3β 和 E-cadherin 的水平，并抑制了 β-catenin 的核转位。
蟾毒配基通过抑制 AKT/GSK3β/β-catenin/E-cadherin 信号通路，是一种有潜力的抗 HCC 治疗候选药物。在 HCC 患者中，特别是在疾病晚期的患者中，进一步研究蟾毒配基是必要的。
