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

doi:10.1016/j.canlet.2007.11.011

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 journal › Article › peer-review

26 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 language	English
Pages (from-to)	205-214
Number of pages	10
Journal	Cancer letters
Volume	261
Issue number	2
DOIs	https://doi.org/10.1016/j.canlet.2007.11.011
Publication status	Published - 2008 Mar 18
Externally published	Yes

Keywords

Combination gene therapy
HSV-tk
MDR1
shRNA

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.canlet.2007.11.011

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

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.",

keywords = "Combination gene therapy, HSV-tk, MDR1, shRNA",

author = "Park, {Seung Yoon} and Wan Lee and Jaetae Lee and Kim, {In San}",

note = "Funding 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. Copyright: Copyright 2008 Elsevier B.V., All rights reserved.",

year = "2008",

month = mar,

day = "18",

doi = "10.1016/j.canlet.2007.11.011",

language = "English",

volume = "261",

pages = "205--214",

journal = "Cancer Letters",

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AU - Park, Seung Yoon

AU - Lee, Wan

AU - Lee, Jaetae

AU - Kim, In San

N1 - Funding 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. Copyright: Copyright 2008 Elsevier B.V., All rights reserved.

PY - 2008/3/18

Y1 - 2008/3/18

N2 - 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.

AB - 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.

KW - Combination gene therapy

KW - HSV-tk

KW - MDR1

KW - shRNA

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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