Down-Regulation of Mcl-1 by Small Interference RNA Induces Apoptosis and Sensitizes HL-60 Leukemia Cells to Etoposide

Karami, Hadi; Baradaran, Behzad; Esfehani, Ali; Sakhinia, Masoud; Sakhinia, Ebrahim

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자료유형: 학술저널

저자정보: Karami, Hadi (Immunology Research Center, Department of Medical Immunology, Faculty of Medicine, Tabriz University of Medical Sciences) Baradaran, Behzad (Immunology Research Center, Department of Medical Immunology, Faculty of Medicine, Tabriz University of Medical Sciences) Esfehani, Ali (Hematology and Oncology Research Center, Shahid Ghazi Hospital, Tabriz University of Medical Sciences) Sakhinia, Masoud (Faculty of Medicine, University of Liverpool) Sakhinia, Ebrahim (Tuberculosis and Lung Diseases Research Centre, Department of Medical Genetics, Faculty of Medicine, Tabriz Genetic Analysis Centre, Tabriz University of Medical Sciences)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제15권 제2호

발행연도: 2014.1

수록면: 629 - 635 (7page)

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Background: Acute myeloid leukemia (AML) is a fatal hematological malignancy which is resistant to a variety of chemotherapy drugs. Myeloid cell leukemia-1 (Mcl-1), a death-inhibiting protein that regulates apoptosis, has been shown to be overexpressed in numerous malignancies. In addition, it has been demonstrated that the expression level of the Mcl-1 gene increases at the time of leukemic relapse following chemotherapy. The aim of this study was to target Mcl-1 by small interference RNA (siRNA) and analyze its effects on survival and chemosensitivity of acute myeloid leukemia cell line HL-60. Materials and Methods: siRNA transfection was performed with a liposome approach. The expression levels of mRNA and protein were measured by real-time quantitative PCR and Western blot analysis, respectively. Trypan blue assays were performed to evaluate tumor cell growth after siRNA transfection. The cytotoxic effects of Mcl-1 siRNA (siMcl-1) and etoposide were determined using MTT assay on their own and in combination. Apoptosis was quantified using a DNA-histone ELISA assay. Results: Transfection with siMcl-1 significantly suppressed the expression of Mcl-1 mRNA and protein in a time-dependent manner, resulting in strong growth inhibition and spontaneous apoptosis. Surprisingly, pretreatment with siMcl-1 synergistically enhanced the cytotoxic effect of etoposide. Furthermore, Mcl-1 down-regulation significantly increased apoptosis sensitivity to etoposide. No significant biological effects were observed with negative control siRNA treatment. Conclusions: Our results suggest that specific suppression of Mcl-1 by siRNA can effectively induce apoptosis and overcome chemoresistance of leukemic cells. Therefore, siMcl-1 may be a potent adjuvant in leukemia chemotherapy.

#Mcl-1 #apoptosis #siRNA #etoposide #leukemia #HL-60

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Karami, Hadi

소속기관 Immunology Research Center, Department of Medical Immunology, Faculty of Medicine, Tabriz University