title: Anti-apoptotic effect of hepatocyte growth factor from actinomycin D in hepatocyte-derived HL7702 cells is associated with activation of PI3K/Akt signaling.
abstract: Actinomycin D (ActD) is a well-known cytotoxic chemotherapeutic reagent and the prevention of ActD-induced apoptotic cell death has been an attractive issue for biomedical investigators. Since phosphatidylinositol-3 kinase (PI3K)/Akt pathway is essential for cell survival, the present study has examined whether the preventive effect of hepatocyte growth factor (HGF) on ActD-induced apoptotic cell death in a human hepatocyte-derived cell line (HL7702) is associated with PI3K/Akt activation. Apoptotic cell death was measured by several methods including Hoechst 33342 staining, DNA fragmentation, and flow cytometry. We found that ActD caused a significant increase in apoptotic cell death, an effect significantly prevented by pre-addition of HGF in the cultures. HGF was found to significantly activate Akt phosphorylation while pre-treatment with PI3K specific inhibitor wortmannin further enhanced ActD-induced apoptotic effect, and also significantly prevented HGF's protection against ActD-induced apoptosis. These results suggest that HGF's prevention of ActD-induced apoptotic cell death in HL7702 cells is associated with the activation of PI3K/Akt signaling.
authors.affiliation: School of Pharmacy, Wenzhou Medical College, Wenzhou, PR China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Li
authors.forename: Shaohui
authors.initials: S
authors.lastname: Cai
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D053938:DNA Fragmentation; D003609:Dactinomycin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004338:Drug Combinations; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011500:Protein Synthesis Inhibitors / Q000633:toxicity*; D015398:Signal Transduction; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D003609:Dactinomycin; D004338:Drug Combinations; D017228:Hepatocyte Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011500:Protein Synthesis Inhibitors; D000077191:Wortmannin