PMID- 26459571
OWN - NLM
STAT- MEDLINE
DCOM- 20160907
LR  - 20211203
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 47
IP  - 6
DP  - 2015 Dec
TI  - Combined antitumor gene therapy with herpes simplex virus-thymidine kinase and 
      short hairpin RNA specific for mammalian target of rapamycin.
PG  - 2233-9
LID - 10.3892/ijo.2015.3194 [doi]
AB  - A proof-of-concept study is presented using dual gene therapy that employed a 
      small hairpin RNA (shRNA) specific for mammalian target of rapamycin (mTOR) and a 
      herpes simplex virus-thymidine kinase (HSV-TK) gene to inhibit the growth of 
      tumors. Recombinant adeno-associated virus (rAAV) vectors containing a mutant TK 
      gene (sc39TK) were transduced into HeLa cells, and the prodrug ganciclovir (GCV) 
      was administered to establish a suicide gene-therapy strategy. Additionally, rAAV 
      vectors expressing an mTOR-targeted shRNA were employed to suppress 
      mTOR-dependent tumor growth. GCV selectively induced death in tumor cells 
      expressing TK, and the mTOR-targeted shRNA altered the cell cycle to impair tumor 
      growth. Combining the TK-GCV system with mTOR inhibition suppressed tumor growth 
      to a greater extent than that achieved with either treatment alone. Furthermore, 
      HSV-TK expression and mTOR inhibition did not mutually interfere with each other. 
      In conclusion, gene therapy that combines the TK-GCV system and mTOR inhibition 
      shows promise as a novel strategy for cancer therapy.
FAU - Woo, Ha-Na
AU  - Woo HN
AD  - Department of Microbiology, University of Ulsan College of Medicine, Seoul, 
      Republic of Korea.
FAU - Lee, Won Il
AU  - Lee WI
AD  - Department of Microbiology, University of Ulsan College of Medicine, Seoul, 
      Republic of Korea.
FAU - Kim, Ji Hyun
AU  - Kim JH
AD  - Department of Microbiology, University of Ulsan College of Medicine, Seoul, 
      Republic of Korea.
FAU - Ahn, Jeonghyun
AU  - Ahn J
AD  - Department of Microbiology, University of Ulsan College of Medicine, Seoul, 
      Republic of Korea.
FAU - Han, Jeong Hee
AU  - Han JH
AD  - Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul 
      National University College of Medicine, Seoul, Republic of Korea.
FAU - Lim, Sue Yeon
AU  - Lim SY
AD  - Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul 
      National University College of Medicine, Seoul, Republic of Korea.
FAU - Lee, Won Woo
AU  - Lee WW
AD  - Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul 
      National University College of Medicine, Seoul, Republic of Korea.
FAU - Lee, Heuiran
AU  - Lee H
AD  - Department of Microbiology, University of Ulsan College of Medicine, Seoul, 
      Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151008
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Antiviral Agents)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Viral Proteins)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.21 (Thymidine Kinase)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - P9G3CKZ4P5 (Ganciclovir)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - Antiviral Agents/pharmacology
MH  - Blotting, Western
MH  - Dependovirus
MH  - Ganciclovir/pharmacology
MH  - Genes, Transgenic, Suicide
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors
MH  - HeLa Cells
MH  - Humans
MH  - Male
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Neoplasms, Experimental/*therapy
MH  - RNA, Small Interfering
MH  - Simplexvirus/*genetics
MH  - TOR Serine-Threonine Kinases/*genetics
MH  - Thymidine Kinase/*genetics
MH  - Transduction, Genetic
MH  - Viral Proteins/*genetics
MH  - Xenograft Model Antitumor Assays
EDAT- 2015/10/16 06:00
MHDA- 2016/09/08 06:00
CRDT- 2015/10/14 06:00
PHST- 2015/07/31 00:00 [received]
PHST- 2015/09/25 00:00 [accepted]
PHST- 2015/10/14 06:00 [entrez]
PHST- 2015/10/16 06:00 [pubmed]
PHST- 2016/09/08 06:00 [medline]
AID - 10.3892/ijo.2015.3194 [doi]
PST - ppublish
SO  - Int J Oncol. 2015 Dec;47(6):2233-9. doi: 10.3892/ijo.2015.3194. Epub 2015 Oct 8.