title: Antitumor effect and underlying mechanism of RGD-modified adenovirus mediated IL-24 expression on myeloid leukemia cells.
abstract: Interleukin-24 (IL-24), a member of the IL-10 cytokine gene family, causes growth suppression and apoptosis in various solid tumor cells. However, the effects of IL-24 on hematopoietic malignant cells have not been extensively explored. In this report, we constructed an RGD-engineered recombinant adenoviral vector, Ad.RGD-IL-24, and assessed its effects on human myeloid leukemia cells. Ad vector mediates gene transfer into leukemia cells with high efficiency. Ectopic over-expression of IL-24 has significant growth inhibition and differentiation inducement effects on these cells. Treatment with Ad.RGD-IL-24 could potentially induce leukemia cells' cell-cycle arrest. In addition, IL-24 expression could significantly induce apoptosis of the THP-1 cells. Ad.RGD-IL-24 had a potent effect on the up-regulation of the expression of GRP78/Bip, GADD34 and Bax, down-regulation of the expression of Bcl-2 and Mcl-1, and induced the activation of Caspase-3, which may be responsible for its apoptosis-inducing effect on THP-1 cells. Furthermore, IL-24 expression could retard transplanted leukemia cell tumor growth in vivo in athymic nude mice. These findings showed the marked antitumor activity of IL-24 and provided potential perspectives in designing therapeutic or vaccine strategies in immuno-gene therapy of myeloid leukemia.
authors.affiliation: Blood Transfusion Research Institute, Wuxi Red Cross Blood Center, Wuxi, Jiangsu 214021, PR China; Medical Biotechnology Institute, Soochow University, Suzhou, Jiangsu 215007, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.affiliation: Blood Transfusion Research Institute, Wuxi Red Cross Blood Center, Wuxi, Jiangsu 214021, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xia
authors.affiliation: Medical Biotechnology Institute, Soochow University, Suzhou, Jiangsu 215007, PR China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.affiliation: Miami University, Oxford, OH 45056, United States.
authors.forename: Julie
authors.initials: J
authors.lastname: Blumenfeld
authors.affiliation: Medical Biotechnology Institute, Soochow University, Suzhou, Jiangsu 215007, PR China.
authors.forename: Biao
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Medical Biotechnology Institute, Soochow University, Suzhou, Jiangsu 215007, PR China.
authors.forename: Jicheng
authors.initials: J
authors.lastname: Yang
authors.affiliation: Medical Biotechnology Institute, Soochow University, Suzhou, Jiangsu 215007, PR China.
authors.forename: Jingcheng
authors.initials: J
authors.lastname: Miao
authors.affiliation: Medical Biotechnology Institute, Soochow University, Suzhou, Jiangsu 215007, PR China. Electronic address: szguzj@163.com.
authors.forename: Zong-Jiang
authors.initials: ZJ
authors.lastname: Gu
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D015316:Genetic Therapy; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000473:pathology / Q000628:therapy*; D008819:Mice, Nude; D009842:Oligopeptides / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D047368:Tumor Burden; D000099180:Interleukin-24
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D007378:Interleukins; D009842:Oligopeptides; D012333:RNA, Messenger; D000099180:Interleukin-24; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse; C047981:arginyl-glycyl-aspartic acid
keywords: Adenovirus; Gene therapy; IL-24; Myeloid leukemia; RGD