Combined antitumor gene therapy with herpes simplex virus-thymidine kinase and short hairpin RNA specific for mammalian target of rapamycin

Ha Na Woo, Won Il Lee, Ji Hyun Kim, Jeonghyun Ahn, Jeong Hee Han, Sue Yeon Lim, Won Woo Lee, Heuiran Lee

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

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 mTORtargeted 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.

Original languageEnglish (US)
Pages (from-to)2233-2239
Number of pages7
JournalInternational Journal of Oncology
Volume47
Issue number6
DOIs
StatePublished - Dec 1 2015
Externally publishedYes

Keywords

  • Mammalian target of rapamycin
  • Recombinant adenoassociated virus
  • Small hairpin RNA
  • Suicide gene therapy
  • Thymidine kinase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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