Combination gene therapy using multidrug resistance (MDR1) gene shRNA and herpes simplex virus-thymidine kinase

Seung Yoon Park, Wan Lee, Jaetae Lee, In-San Kim

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The current study was designed to evaluate the anti-tumor effects of MDR1 shRNA in combination with herpes simplex virus-thymidine kinase/ganciclovir (HSV-tk/GCV) suicide gene therapy system. Introduction of an MDR1-targeted small hairpin RNA (shMDR) markedly enhanced the intracellular accumulation of and increased sensitivity to drugs transported by P-glycoprotein. Functional TK-eGFP fusion protein expression was confirmed by Western blot analysis and ganciclovir uptake assay. Compared with GCV or doxorubicin alone, the combination of anti-cancer drug chemotherapy with GCV administration displays additive cytotoxicity in shMDR1-TK-eGFP expressing cells. These results for the first time suggest the potential of combination gene therapy using suicide gene therapy and RNAi-based gene therapy in vitro.

Original languageEnglish
Pages (from-to)205-214
Number of pages10
JournalCancer letters
Volume261
Issue number2
DOIs
Publication statusPublished - 2008 Mar 18
Externally publishedYes

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Keywords

  • Combination gene therapy
  • HSV-tk
  • MDR1
  • shRNA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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