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 language | English |
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Pages (from-to) | 205-214 |
Number of pages | 10 |
Journal | Cancer letters |
Volume | 261 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2008 Mar 18 |
Externally published | Yes |
Keywords
- Combination gene therapy
- HSV-tk
- MDR1
- shRNA
ASJC Scopus subject areas
- Oncology
- Cancer Research