title: Ethyl acetate extract from Jiedu Xiaozheng Yin inhibits the proliferation of human hepatocellular carcinoma cells by suppressing polycomb gene product Bmi1 and Wnt/β-catenin signaling.
abstract: Jiedu Xiaozheng Yin (JXY) is a Chinese herbal decoction used to treat hepatocellular carcinoma (HCC). Previous studies have demonstrated that JXY can inhibit HCC cell proliferation via induction of G0/G1 phase arrest. In this study, we investigated whether the inhibitory effect of JXY on HCC cells is associated with the inhibition of the Wnt/β‑catenin pathway and the polycomb gene product Bmi1. Ethyl acetate extract from JXY (EE-JXY) was prepared. Methyl thiazolyl tetrazolium (MTT) and colony formation assays were used to measure cell proliferation. Immunofluorescence was used to analyze the expression and location of β-catenin and Bmi1. Immunohistochemistry was used to examine the expression of proliferating cell nuclear antigen (PCNA), c-myc and cyclin D1. β-catenin, Bmi1, c-myc, cyclin D1 and p16INK4A mRNA levels were detected by RT-PCR. The results demonstrated that EE-JXY inhibited the expression of PCNA, c-myc, cyclin D1 and Bmi1, and upregulated the expression of p16INK4A. We also found that EE-JXY could facilitate β-catenin translocation from the cytoplasm and nuclei to the cytomembrane. Finally, suppression of cell proliferation and expression of Bmi1 and Wnt/β-catenin by EE-JXY was confirmed in a mouse xenograft model of HCC. Thus, EE-JXY can inhibit the proliferation of HCC partially via suppression of the Bmi1 and Wnt/β-catenin signaling pathways.
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Xu-Zheng
authors.initials: XZ
authors.lastname: Chen
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Zhi-Yun
authors.initials: ZY
authors.lastname: Cao
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Jin-Nong
authors.initials: JN
authors.lastname: Li
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Hu
authors.affiliation: The Second Affiliated Hospital, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350003, P.R. China.
authors.forename: You-Quan
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Yun-Mei
authors.initials: YM
authors.lastname: Huang
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Zhi-Zhen
authors.initials: ZZ
authors.lastname: Liu
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Lian-Ming
authors.initials: LM
authors.lastname: Liao
authors.affiliation: The Second Affiliated Hospital, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350003, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Du
mesh_terms: D000085:Acetates / Q000737:chemistry; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051379:Mice; D063150:Polycomb Repressive Complex 1 / Q000096:biosynthesis*; D060449:Wnt Signaling Pathway / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000085:Acetates; C069077:BMI1 protein, human; D004365:Drugs, Chinese Herbal; C587679:Jiedu Xiaozheng Yin; C007650:ethyl acetate; D063150:Polycomb Repressive Complex 1