title: Tanshinone IIA promotes the proliferation of WB-F344 hepatic oval cells via Wnt/β-catenin signaling.
abstract: Tanshinone IIA (TSA) is a widely used traditional Chinese medicine, which has been demonstrated to protect damaged liver cells and is currently administered in the treatment of liver fibrosis. Liver precursor cells, also termed oval cells, are key in the repair of liver tissues following injury. However, whether TSA improves the function of liver cells and protects the liver from injury by enhancing the growth and proliferation of hepatic oval cells remains to be elucidated. In the present study, low to moderate concentrations of TSA were observed to stimulate proliferation, did not induce apoptosis in WB-F344 rat hepatic oval cells and the increased expression levels of β-catenin. WB-F344 cells were treated with various concentrations of TSA (0-80 µg/ml) for 24, 48, 72 and 96 h. Cell proliferation was measured using a Cell Counting kit-8 (CCK-8) assay, a 5-ethynyl-2'-deoxyuridine assay and a carboxyfluorescein diacetate succinimidyl ester (CFSE) assay. The CCK-8 assay demonstrated that treatment of WB-F344 cells with 20-40 µg/ml TSA for up to 72 h significantly increased proliferation. Similar results were observed in the subsequent EdU and CFSE assays. Furthermore, a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay demonstrated that 20-40 µg/ml TSA treatment for up to 96 h did not induce apoptosis of the WB-F344 cells. Notably, the results of western blot, immunofluorescence and reverse transcription-quantitative polymerase chain reaction analyses demonstrated that treatment of the WB-F344 cells with 20-40 µg/ml TSA for up to 72 h significantly increased the expression levels of β-catenin. These data indicated that TSA at concentrations between 20 and 40 µg/ml may induce WB-F344 cell proliferation by activating the canonical Wnt signaling pathway. The results of the present study suggest that TSA may be a useful natural agent to enhance repair and regeneration of the injured liver, and improve liver regeneration following orthotopic liver transplantation.
authors.affiliation: Liver Disease Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Xingyu
authors.initials: X
authors.lastname: Ze
authors.affiliation: Liver Disease Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Jidong
authors.initials: J
authors.lastname: Jia
authors.affiliation: Liver Disease Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Xinmin
authors.initials: X
authors.lastname: Li
authors.affiliation: Liver Disease Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: You
authors.affiliation: Liver Disease Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Liver Disease Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Integrated Traditional and Western Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Baoen
authors.initials: B
authors.lastname: Wang
mesh_terms: D045784:Abietanes / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D045784:Abietanes; D012333:RNA, Messenger; D051176:beta Catenin; C021751:tanshinone