Institute of Biomedical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, China; Department of Laboratory Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
Dig Liver Dis. 2019 Jan;51(1):120-126. doi: 10.1016/j.dld.2018.06.012. Epub 2018 Jun 21.
The aim of this study is to investigate the role of glypican-3(GPC3)/wnt/β-catenin signaling pathway and autophagy in the regulation of hepatocellular carcinoma (HCC) growth mediated by curcumin.
HepG2 cells were treated with various concentrations of curcumin and/or GPC3-targeting siRNA in the presence or absence of 3-MA. Cell proliferation and apoptosis were determined by MTT and TUNEL assay, respectively. Expression of GPC3, β-catenin, c-myc, LC3, and Beclin1 was determined by western blotting. In addition, curcumin was tested in tumor xenografts mice model, Caliper IVIS Lumina II was used to monitor the tumor growth, and GPC3/wnt/β-catenin signaling proteins were determined by western blotting.
Curcumin treatment led to proliferation inhibition and apoptosis induction in HepG2 cells in a concentration-dependent manner, and suppressed HCC tumor growth in vivo. Further analysis showed that curcumin treatment inactivated Wnt/β-catenin signaling and decreased GPC3 expression, silencing of GPC3 expression promoted the effects of curcumin on Wnt/β-catenin signaling. In addition, inhibiting autophagy by 3-MA relieved curcumin-dependent down-regulation of GPC3.
Curcumin suppressed HCC tumor growth through down-regulating GPC3/wnt/β-catenin signaling pathway, which was partially mediated by activation of autophagy.
本研究旨在探讨甘胆酸-3（GPC3）/Wnt/β-连环蛋白信号通路和自噬在姜黄素调控肝细胞癌（HCC）生长中的作用。
用不同浓度的姜黄素和/或 GPC3 靶向 siRNA 处理 HepG2 细胞，并在存在或不存在 3-MA 的情况下进行处理。通过 MTT 和 TUNEL 分析分别测定细胞增殖和凋亡。通过 Western blot 测定 GPC3、β-连环蛋白、c-myc、LC3 和 Beclin1 的表达。此外，在肿瘤异种移植小鼠模型中测试姜黄素，使用 Caliper IVIS Lumina II 监测肿瘤生长，并通过 Western blot 测定 GPC3/Wnt/β-连环蛋白信号蛋白。
姜黄素处理以浓度依赖性方式导致 HepG2 细胞增殖抑制和凋亡诱导，并抑制体内 HCC 肿瘤生长。进一步分析表明，姜黄素处理使 Wnt/β-连环蛋白信号失活并降低 GPC3 表达，沉默 GPC3 表达促进了姜黄素对 Wnt/β-连环蛋白信号的作用。此外，通过 3-MA 抑制自噬可减轻姜黄素依赖的 GPC3 下调。
姜黄素通过下调 GPC3/Wnt/β-连环蛋白信号通路抑制 HCC 肿瘤生长，部分通过自噬的激活介导。
