PMID- 26935255
OWN - NLM
STAT- MEDLINE
DCOM- 20161228
LR  - 20231213
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 13
IP  - 4
DP  - 2016 Apr
TI  - Connexin32‑mediated antitumor effects of suicide gene therapy against 
      hepatocellular carcinoma: In vitro and in vivo anticancer activity.
PG  - 3213-9
LID - 10.3892/mmr.2016.4895 [doi]
AB  - 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.
FAU - Wu, Lun
AU  - Wu L
AD  - Department of Hepatobiliary Surgery, Experiment Center of Medicine, Dongfeng 
      Hospital, Hubei University of Medicine, Shiyan, Hubei 442001, P.R. China.
FAU - Zhou, Wen-Bo
AU  - Zhou WB
AD  - Department of Hepatobiliary Surgery, Experiment Center of Medicine, Dongfeng 
      Hospital, Hubei University of Medicine, Shiyan, Hubei 442001, P.R. China.
FAU - Shen, Feng
AU  - Shen F
AD  - Department of Hepatobiliary Surgery, Experiment Center of Medicine, Dongfeng 
      Hospital, Hubei University of Medicine, Shiyan, Hubei 442001, P.R. China.
FAU - Liu, Wei
AU  - Liu W
AD  - Department of Obstetrics, Haikou Hospital of Maternal and Child Health, Haikou, 
      Hainan 570100, P.R. China.
FAU - Wu, Hong-Wei
AU  - Wu HW
AD  - Department of Hepatobiliary Surgery, Experiment Center of Medicine, Dongfeng 
      Hospital, Hubei University of Medicine, Shiyan, Hubei 442001, P.R. China.
FAU - Zhou, Shi-Ji
AU  - Zhou SJ
AD  - Department of Gastrointestinal Surgery, The Second Affiliated Hospital of 
      Chongqing Medical University, Chongqing 400010, P.R. China.
FAU - Li, Sheng-Wei
AU  - Li SW
AD  - Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing 
      Medical University, Chongqing 400010, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160216
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Connexins)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 2.7.1.21 (Thymidine Kinase)
RN  - P9G3CKZ4P5 (Ganciclovir)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology/therapeutic use
MH  - Apoptosis/*drug effects
MH  - Blotting, Western
MH  - Bystander Effect
MH  - Carcinoma, Hepatocellular/drug therapy/metabolism/pathology
MH  - Connexins/genetics/*metabolism
MH  - Ganciclovir
MH  - Hep G2 Cells
MH  - Humans
MH  - Liver Neoplasms/drug therapy/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Simplexvirus/genetics
MH  - Thymidine Kinase/genetics
MH  - Transfection
MH  - Transplantation, Heterologous
MH  - Tretinoin/*pharmacology/therapeutic use
MH  - Gap Junction beta-1 Protein
EDAT- 2016/03/05 06:00
MHDA- 2016/12/29 06:00
CRDT- 2016/03/04 06:00
PHST- 2015/03/04 00:00 [received]
PHST- 2016/01/07 00:00 [accepted]
PHST- 2016/03/04 06:00 [entrez]
PHST- 2016/03/05 06:00 [pubmed]
PHST- 2016/12/29 06:00 [medline]
AID - 10.3892/mmr.2016.4895 [doi]
PST - ppublish
SO  - Mol Med Rep. 2016 Apr;13(4):3213-9. doi: 10.3892/mmr.2016.4895. Epub 2016 Feb 16.