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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2014.1
- 수록면
- 114 - 121 (8page)
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Refractoriness of acute myeloid leukemia (AML) cells to chemotherapeutics represents a major clinical barrier. Suicide gene therapy for cancer has been attractive but with limited clinical efficacy. In this study, we investigated the potential application of herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) based system to inhibit chemoresistant AML cells. We first generated Ara-C resistant K562 cells and doxorubicin-resistant THP-1 cells. We found that the HSV-TK/GCV anticancer system suppressed drug resistant leukemic cells in culture. Chemoresistant AML cell lines displayed similar sensitivity to HSV-TK/GCV. Moreover, HSV-TK/GCV killing of leukemic cells was augmented to a mild but significant extent by all-trans retinoic acid (ATRA) with concomitant upregulation of Connexin 43, a major component of gap junctions. Interestingly, HSV-TK/GCV killing was enhanced by expression of vesicular stomatitis virus G glycoprotein (VSV-G), a fusogenic membrane protein, which also increased leukemic cell fusion. Co-culture resistant cells expressing HSV-TK and cells stably transduced with VSV-G showed that expression of VSV-G could promote the bystander killing effect of HSV-TK/GCV. Furthermore, combination of HSV-TK/GCV with VSV-G plus ATRA produced more pronounced antileukemia effect. These results suggest that the HSV-TK/GCV system in combination with fusogenic membrane proteins and/or ATRA could provide a strategy to mitigate the chemoresistance of AML.
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참고문헌 (38)
참고문헌 신청
Asklund, T / 2003 / Gapjunction-mediated bystander effect in primary cultures of humanmalignant gliomas with recombinant expression of the HSVtk gene / Exp. Cell Res 284:185~195
Aiuti, A / 2013 / Lentiviral hematopoietic stem cell gene therapy in patients withWiskott-Aldrich syndrome / Science 341:1233151
Braun, S. E / 1997 / Genetherapy strategies for leukemia / Mol. Med 3:39~46
Blumenthal, M / 2007 / Effective suicide gene therapy for leukemiain a model of insertional oncogenesis in mice / Mol. Ther 15:183~192
Bondanza, A / 2011 / IL-7 receptor expression identifiessuicide gene-modified allospecific CD8+ T cells capable ofself-renewal and differentiation into antileukemia effectors / Blood 117:6469~6478
Aiuti, A / 2013 / Lentiviral hematopoietic stem cell gene therapy in patients withWiskott-Aldrich syndrome / Science 341:1233151
Braun, S. E / 1997 / Genetherapy strategies for leukemia / Mol. Med 3:39~46
Blumenthal, M / 2007 / Effective suicide gene therapy for leukemiain a model of insertional oncogenesis in mice / Mol. Ther 15:183~192
Bondanza, A / 2011 / IL-7 receptor expression identifiessuicide gene-modified allospecific CD8+ T cells capable ofself-renewal and differentiation into antileukemia effectors / Blood 117:6469~6478
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