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: Xin Yu, Wei Xia, Shuai Li, Julie Blumenfeld, Biao Zhang, Jicheng Yang, Jingcheng Miao, Zong-Jiang Gu
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 28 Issue 1 Pg. 560-70 (Sep 2015) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 26225923 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Endoplasmic Reticulum Chaperone BiP
• HSPA5 protein, human
• Hspa5 protein, mouse
• Interleukins
• Oligopeptides
• RNA, Messenger
• interleukin-24
• arginyl-glycyl-aspartic acid

Topics

• Adenoviridae (genetics)
• Animals
• Apoptosis
• Cell Cycle
• Cell Differentiation
• Cell Line, Tumor
• Endoplasmic Reticulum Chaperone BiP
• Genetic Therapy
• Humans
• Interleukins (genetics)
• Leukemia, Myeloid (pathology, therapy)
• Mice, Nude
• Oligopeptides (genetics)
• RNA, Messenger (metabolism)
• Tumor Burden