title: Connexin32‑mediated antitumor effects of suicide gene therapy against hepatocellular carcinoma: In vitro and in vivo anticancer activity.
abstract: Normal hepatocytes express connexin32 (Cx32), which forms gap junctions at cell‑cell contact areas. The aim of the present study was to investigate whether Cx32 mediates the cell death‑inducing effects of ultrasound microbubbles carrying the herpes simplex virus thymidine kinase (HSV‑TK) suicide gene against hepatocellular carcinoma cells in vitro and in vivo. HepG2 cells were exposed to different concentrations of trans‑retinoic acid (ATRA) in culture, to evaluate the intrinsic antitumor effect of ATRA. Detailed in‑vitro and in‑vivo investigations on the antitumor effects of ATRA via Cx32 mediation were performed, and the possible underlying mechanisms of action of the compound were then examined. The gene expression of HSV‑TK transfected by ultrasound wave irradiation in the HepG2 cells was quantified using reverse transcription‑quantitative polymerase chain reaction analysis. The effects on cell death were assessed using an MTT assay. The protein expression levels of Cx32 in ATRA‑untreated or ATRA‑treated tissues were quantified by immunohistochemical analysis and Western blot assays. The HSV‑TK gene was successfully transfected into the HepG2 cell using ultrasound wave irradiation, and was stably expressed. Compared with the other groups, the HSV‑TK gene group treated with ATRA exhibited an increased number of apoptotic cells (P<0.05) and improved tumor suppression (P<0.05). ATRA significantly increased the expression of Cx32 in the hepatoma tissues (P<0.01). The present study demonstrated that ATRA elevated the protein expression of Cx32 and enhanced the bystander effect of the HSV‑TK/GCV suicide gene therapy system, which may provide a potential strategy for hepatocellular carcinoma treatment.
authors.affiliation: Department of Hepatobiliary Surgery, Experiment Center of Medicine, Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei 442001, P.R. China.
authors.forename: Lun
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Hepatobiliary Surgery, Experiment Center of Medicine, Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei 442001, P.R. China.
authors.forename: Wen-Bo
authors.initials: WB
authors.lastname: Zhou
authors.affiliation: Department of Hepatobiliary Surgery, Experiment Center of Medicine, Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei 442001, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Shen
authors.affiliation: Department of Obstetrics, Haikou Hospital of Maternal and Child Health, Haikou, Hainan 570100, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, Experiment Center of Medicine, Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei 442001, P.R. China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Wu
authors.affiliation: Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Shi-Ji
authors.initials: SJ
authors.lastname: Zhou
authors.affiliation: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Sheng-Wei
authors.initials: SW
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D024201:Bystander Effect; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D015774:Ganciclovir; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018139:Simplexvirus / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics; D014162:Transfection; D014183:Transplantation, Heterologous; D014212:Tretinoin / Q000494:pharmacology* / Q000627:therapeutic use; D000097002:Gap Junction beta-1 Protein
chemical_list: D000970:Antineoplastic Agents; D017630:Connexins; D015774:Ganciclovir; D013937:Thymidine Kinase; D014212:Tretinoin; D000097002:Gap Junction beta-1 Protein