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.
Bibliographical noteFunding Information:
We thank Dr. Jae Yong Park (Kyungpook National University, Daegu, Korea) for the kind donation of HSV-tk expression construct. This study was supported by the Grant No. RTI04-01-01 from the Regional Technology Innovation Program of the MOCIE, Advanced Medical Technology Cluster for Diagnosis and Prediction at Kyungpook National University from MOCIE; a grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (0720550-2); and by the Brain Korea 21 Project in 2007.
- Combination gene therapy
ASJC Scopus subject areas
- Cancer Research