title: In vivo and in vitro inhibition of human liver cancer progress by downregulation of the μ-opioid receptor and relevant mechanisms.
abstract: Opiates have long been used as analgesics to relieve pain associated with various medical conditions. μ-opioid receptor (MOR) is the main member of the opioid receptor super-family and the excitation or overexpression of MOR promotes the proliferation of many kinds of tumor cells. It was found in our previous studies that MOR was highly expressed in the tissue and cells of human liver cancer. However, the impact of MOR on the progress of human liver cancer remains unknown. The purpose of this study is to investigate the impact of MOR downregulation on the progress of human liver cancer and the mechanisms involved. RNA interfering or specific inhibitor was administered to downregulate the MOR in human hepato-cellular carcinoma cells and it was found that the proliferation of hepatocellular carcinoma cells was significantly inhibited with the increase of the apoptotic rate, while the cell cycle was blocked in G0/G1 phase and the tumor growth in the mice was retarded. In addition, downregulation of MOR resulted in the increase of phosphorylation of the MKK7 expression and JNK activation. On the contrary, blockade of MKK7 pathway can reverse the antitumor role of MOR. In summary, downregulation of MOR is able to inhibit both in vivo and in vitro human liver cancer progress and it shows potential to be used in cancer therapy.
authors.affiliation: Department of Hematology and Oncology, First Hospital, Jilin University, Changchun 130021, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Lu
authors.forename: Zefeng
authors.initials: Z
authors.lastname: Liu
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhao
authors.forename: Huimin
authors.initials: H
authors.lastname: Tian
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Liu
authors.forename: Changji
authors.initials: C
authors.lastname: Yuan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D004789:Enzyme Activation / Q000235:genetics; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D048688:MAP Kinase Kinase 7 / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D008819:Mice, Nude; D010766:Phosphorylation / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D017450:Receptors, Opioid, mu; D048031:JNK Mitogen-Activated Protein Kinases; D048688:MAP Kinase Kinase 7; C482569:MAP2K7 protein, human