Inhibition of autophagy induced by overexpression of mda-7/interleukin-24 strongly augments the antileukemia activity in vitro and in vivo
文献类型：期刊论文
| 作者 | Yang, C; Tong, Y; Ni, W; Liu, J; Xu, W; Li, L; Liu, X; Meng, H; Qian, W |
| 刊名 | CANCER GENE THERAPY
 |
| 出版日期 | 2010 |
| 卷号 | 17期号:2页码:109-119 |
| 关键词 | mda-7 interleukin-24 autophagy Beclin-1 replication-competent adenovirus phosphatidylinositol 3-kinase inhibitor |
| 通讯作者 | Qian, W (reprint author), Zhejiang Univ, Coll Med, Affiliated Hosp 1, Minist Publ Hlth,Inst Hematol,Key Lab Combined Mu, 79 Qingchun Rd, Hangzhou 310003, Zhejiang, Peoples R China.,qianwenb@Yahoo.com.cn |
| 英文摘要 | Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) is a novel candidate of tumor suppressor that can selectively induce apoptosis experimentally in a spectrum of human cancer cells including leukemia cells. However, a recent study suggests that mda-7/IL-24 promotes the survival of chronic lymphocytic leukemia B-cells. In this study, we showed that mda-7/IL-24 was constitutively expressed in leukemia cell lines and primary acute myeloid leukemia samples. Using a conditionally replicating adenovirus expressing mda-7/IL-24 (ZD55-IL-24), we showed that enforced expression of mda-7/IL-24 in leukemia cells induced autophagy, which was triggered by the upregulation of Beclin-1. Immunofluorescence and coimmunoprecipitation studies suggested that mda-7/IL-24 protein interacts with Beclin-1. Class III PI3K/Beclin-1 complex was shown involved in the mda-7/IL-24-induced autophagy. Moreover, autophagy inhibition by phosphatidylinositol 3-kinase inhibitor, wortmannin, resulted in a reduced Beclin-1 expression and autophagosome formation associated with significantly enhanced cell death. Importantly, the combination of ZD55-IL-24 with wortmannin elicited a strongly enhanced antileukemia efficacy in established leukemia xenografts. These results suggest that mda-7/IL-24-induced autophagy in leukemia cells may provide survival advantage and mda-7/IL-24 combined with agents that disrupt autophagy is a promising new strategy for the treatment of leukemia. Cancer Gene Therapy (2010) 17, 109-119; doi:10.1038/cgt.2009.57; published online 4 September 2009 |
| 学科主题 | Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine |
| 类目[WOS] | Biotechnology & Applied Microbiology ; Oncology ; Genetics & Heredity ; Medicine, Research & Experimental |
| 关键词[WOS] | MALIGNANT GLIOMA-CELLS ; DIFFERENTIATION-ASSOCIATED GENE-7 ; CONDITIONALLY REPLICATING ADENOVIRUS ; TUMOR-SUPPRESSOR ACTIVITY ; BREAST-CANCER CELLS ; HUMAN LUNG-CANCER ; MELANOMA-DIFFERENTIATION ; MDA-7 EXPRESSION ; ARSENIC TRIOXIDE ; ANTITUMOR-ACTIVITY |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000273496200005 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/955]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Yang, C,Tong, Y,Ni, W,et al. Inhibition of autophagy induced by overexpression of mda-7/interleukin-24 strongly augments the antileukemia activity in vitro and in vivo[J]. CANCER GENE THERAPY,2010,17(2):109-119. |
| APA | Yang, C.,Tong, Y.,Ni, W.,Liu, J.,Xu, W.,...&Qian, W.(2010).Inhibition of autophagy induced by overexpression of mda-7/interleukin-24 strongly augments the antileukemia activity in vitro and in vivo.CANCER GENE THERAPY,17(2),109-119. |
| MLA | Yang, C,et al."Inhibition of autophagy induced by overexpression of mda-7/interleukin-24 strongly augments the antileukemia activity in vitro and in vivo".CANCER GENE THERAPY 17.2(2010):109-119. |
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