PMID- 27123081
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1792-1074 (Print)
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Linking)
VI  - 11
IP  - 5
DP  - 2016 May
TI  - A double suicide gene system driven by vascular endothelial growth factor 
      promoter selectively kills human hepatocellular carcinoma cells.
PG  - 3152-3160
AB  - The aim of the present study was to investigate the selective killing effect on 
      hepatocellular carcinoma (HCC) cells of an adenovirus (Ad)-mediated cytosine 
      deaminase (CD) in combination with thymidine kinase (TK) suicide gene system, 
      driven by the vascular endothelial growth factor promoter (VEGFp), in vitro and 
      in vivo. A double suicide gene system with VEGFp, named Ad-VEGFp-CDglyTK, was 
      constructed and transfected into human HCC cells (BEL-7402 or HepG2; the latter 
      cell type is deficient in VEGF) and human umbilical vein vascular endothelial 
      cells (HUVEC). Green fluorescent protein expression was detected by fluoroscopy 
      to verify transfection efficiency, and CDglyTK gene expression was detected by 
      reverse transcription-polymerase chain reaction (PCR). The selective killing 
      effect of Ad-VEGFp-CDglyTK was measured by 
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow 
      cytometry (FCM) in vitro and by xenograft studies in vivo. PCR revealed that the 
      transgenic CDglyTK gene was expressed in BEL-7402 cells and HUVEC, but not in 
      HepG2 cells. The cell survival rate significantly decreased in line with 
      increasing concentrations of the prodrugs, ganciclovir (GCV) alone, 
      5-fluorocytosine (5-FC) alone or a combination of the two, in HUVEC and BEL-7402 
      cells with the transfected CDglyTK gene, but not in untransfected HUVEC or 
      BEL-7402 cells, or in transfected or untransfected HepG2 cells. This result was 
      additionally confirmed by FCM. GCV and 5-FC inhibited the HUVEC and BEL-7402 
      cells containing the transfected CDglyTK gene and also inhibited adjacent 
      unmodified cells via the 'bystander effect'. No similar results were observed in 
      HepG2 cells. Compared with the control group, tumors with the transfected CDglyTK 
      gene were smaller and the microvessel density of the tumor tissue was 
      significantly decreased. It was concluded that a combination TK/GCV and CD/5-FC 
      suicide gene system driven by VEGFp may provide a promising treatment strategy 
      for HCC.
FAU - Wu, Kai
AU  - Wu K
AD  - Department of Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 
      Guangdong 510282, P.R. China.
FAU - Yang, Liucheng
AU  - Yang L
AD  - Department of Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 
      Guangdong 510282, P.R. China.
FAU - Huang, Zonghai
AU  - Huang Z
AD  - Department of Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 
      Guangdong 510282, P.R. China.
FAU - Zhao, Haijun
AU  - Zhao H
AD  - Department of Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 
      Guangdong 510282, P.R. China.
FAU - Wang, Jianjun
AU  - Wang J
AD  - Department of Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 
      Guangdong 510282, P.R. China.
FAU - Xu, Shuai
AU  - Xu S
AD  - Department of Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 
      Guangdong 510282, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20160322
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC4841088
OTO - NOTNLM
OT  - cytosine deaminase/ganciclovir
OT  - hepatocellular carcinoma
OT  - suicide gene
OT  - thymidine kinase/5-fluorocytosine
OT  - vascular endothelial growth factor
EDAT- 2016/04/29 06:00
MHDA- 2016/04/29 06:01
PMCR- 2016/03/22
CRDT- 2016/04/29 06:00
PHST- 2015/01/19 00:00 [received]
PHST- 2016/02/16 00:00 [accepted]
PHST- 2016/04/29 06:00 [entrez]
PHST- 2016/04/29 06:00 [pubmed]
PHST- 2016/04/29 06:01 [medline]
PHST- 2016/03/22 00:00 [pmc-release]
AID - OL-0-0-4360 [pii]
AID - 10.3892/ol.2016.4360 [doi]
PST - ppublish
SO  - Oncol Lett. 2016 May;11(5):3152-3160. doi: 10.3892/ol.2016.4360. Epub 2016 Mar 
      22.