title: [DADLE suppresses the proliferation of human liver cancer HepG2 cells by activation of PKC pathway and elevates the sensitivity to cis-diammine dichloridoplatium].
abstract: OBJECTIVE
  To investigate the effect of DADLE, a δ-opioid receptor agonist, on the proliferation of human liver cancer HepG2 cells and explore the mechanism involving PKC pathway.
  
  
  METHODS
  HepG2 cells were treated with DADLE at different doses (0.01, 0.1, 1.0 and 10 µmol/L). Cell viability was determined using methyl thiazolyl terazolium (MTT) assay. The expression of PKC mRNA and p-PKC protein were examined by RT-PCR and Western blot assay. After treated separately with DADLE plusing NAL or PMA, the cell cycle of HepG2 cells was analyzed by flow cytometer. MTT was used to detect their proliferation capacity and Western blot was used to examine the p-PKC expression. The growth inhibitory rate of HepG2 cells treated with DADLE and cis-diammine dichloridoplatinum (CDDP) was analyzed.
  
  
  RESULTS
  DADLE at different concentrations showed an inhibitory effect on the proliferation of HepG2 cells though inhibiting the expression of PKC mRNA and p-PKC protein. The results of flow cytometry showed that compared with the control group, the percentage of S + G(2)/M cells in DADLE-treated group was lowered by 3.94% (P < 0.01). Meanwhile, after treated with NAL and PMA, the percentage was elevated by 3.22% and 3.63%, respectively (P < 0.01). The MTT and Western blot assays showed that compared with the control group, the values of A570 and p-PKC protein levels in the HepG2 cells of DADLE-treated group were significantly decreased (P < 0.01). After treatment with NAL and PMA, the values of A570 and p-PKC protein levels were elevated significantly (P < 0.01). The growth inhibitory rate of DADLE + CDDP group was 79.9%, significantly lower than 25.2% and 43.2% of the DADLE and CDDP groups, respectively.
  
  
  CONCLUSIONS
  Activation of δ-opioid receptor by DADLE inhibits the apoptosis of human liver cancer HepG2 cells. The underlying mechanism may be correlated with PKC pathway. DADLE can enhance the chemosensitivity of HepG2 cells to CDDP.
authors.affiliation: Department of General Surgery, the Second Affiliated Hospital of Dalian Medical University, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
authors.forename: Jian
authors.initials: J
authors.lastname: DU
authors.forename: Zhen-ming
authors.initials: ZM
authors.lastname: Gao
authors.forename: Rui
authors.initials: R
authors.lastname: Liang
authors.forename: De-guang
authors.initials: DG
authors.lastname: Sun
authors.forename: Xue-li
authors.initials: XL
authors.lastname: Jin
authors.forename: Li-ming
authors.initials: LM
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D016308:Enkephalin, Leucine-2-Alanine / Q000008:administration & dosage / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000819:agonists; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D012333:RNA, Messenger; D017465:Receptors, Opioid, delta; C016658:phorbolol myristate acetate; D009271:Naltrexone; D016308:Enkephalin, Leucine-2-Alanine; D011493:Protein Kinase C; C055382:naltrindole; D013755:Tetradecanoylphorbol Acetate; D002945:Cisplatin