Pei Hu1, Changzheng Ke2, Xingrong Guo3, Pan Ren4, Yaoyao Tong5, Sen Luo6, Yulin He6, Zhiqiang Wei6, Bin Cheng6, Ruiming Li6, Jie Luo7, Zhongji Meng8. 1. Institute of Biomedical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, China; Department of Laboratory Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, China. 2. Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, Shiyan, China. 3. Hubei Key Laboratory of Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, China. 4. Department of Pharmacy, Xiangyang Hospital of Traditional Chinese Medicine, Xiangyang, China. 5. Department of Laboratory Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, China. 6. Institute of Biomedical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, China. 7. Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, China. 8. Institute of Biomedical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, China; Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, Shiyan, China. Electronic address: zhongji.meng@taihehospital.com.
Abstract
AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Curcumin suppressed HCC tumor growth through down-regulating GPC3/wnt/β-catenin signaling pathway, which was partially mediated by activation of autophagy.
AIM: 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. METHODS: 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. RESULTS: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. CONCLUSION:Curcumin suppressed HCC tumor growth through down-regulating GPC3/wnt/β-catenin signaling pathway, which was partially mediated by activation of autophagy.
Authors: Monica Benvenuto; Loredana Albonici; Chiara Focaccetti; Sara Ciuffa; Sara Fazi; Loredana Cifaldi; Martino Tony Miele; Fernando De Maio; Ilaria Tresoldi; Vittorio Manzari; Andrea Modesti; Laura Masuelli; Roberto Bei Journal: Int J Mol Sci Date: 2020-09-10 Impact factor: 5.923
Authors: Man Wang; Shuai Jiang; Li Zhou; Fei Yu; Han Ding; Peifeng Li; Meng Zhou; Kun Wang Journal: Int J Biol Sci Date: 2019-05-07 Impact factor: 6.580