Enhanced growth suppression of Philadephia1 leukemia cells by targeting bcr3/abl2 and VEGF through antisense strategy

X L Cong; B Li; R C Yang; S Z Feng; S J Chen; Z C Han

doi:10.1038/sj.leu.2403851

Enhanced growth suppression of Philadephia1 leukemia cells by targeting bcr3/abl2 and VEGF through antisense strategy

Leukemia. 2005 Sep;19(9):1517-24. doi: 10.1038/sj.leu.2403851.

Authors

X L Cong¹, B Li, R C Yang, S Z Feng, S J Chen, Z C Han

Affiliation

¹ State Key Laboratory of Experimental Hematology, National Research Center for Stem Cell Engineering & Technology, Tianjin, China.

PMID: 16034468
DOI: 10.1038/sj.leu.2403851

Abstract

An antisense strategy by targeting both bcr3/abl2 and VEGF was designed to suppress the growth of Philadephia1 leukemia cells in vitro and in vivo in mice. In vitro, although bcr3/abl2 or VEGF antisense oligodeoxyribonucleotides (AS-ODNs) alone was able to inhibit the proliferation of K562 cells, the combination of bcr3/abl2 and VEGF AS-ODNs produced an additive inhibitory effect on the growth of K562 cells and significantly enhanced the sensibility of K562 cells to apoptosis-inducing stimuli including STI571. In vivo, the nude mice xenografted with K562 cells received intratumoral injections of bcr3/abl2 and VEGF AS-ODNs showed a significant reduction in leukemia tumor size and microvessel density and an increase of apoptosis in the tumors when compared to the mice that received an individual agent. These results demonstrate that targeting both bcr3/abl2 and VEGF can result in an additive tumor-suppressive action and may represent an excellent strategy to augment the efficacy of chemotherapy in CML.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Drug Screening Assays, Antitumor
Female
Fusion Proteins, bcr-abl / drug effects*
Fusion Proteins, bcr-abl / genetics
Fusion Proteins, bcr-abl / metabolism
Gene Expression Regulation, Neoplastic / drug effects
Humans
K562 Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy*
Mice
Mice, Inbred BALB C
Mice, Nude
Neovascularization, Pathologic / pathology
Oligodeoxyribonucleotides, Antisense / pharmacology
RNA, Messenger / drug effects
RNA, Messenger / genetics
Vascular Endothelial Growth Factor A / drug effects*
Vascular Endothelial Growth Factor A / genetics
Vascular Endothelial Growth Factor A / metabolism
Xenograft Model Antitumor Assays

Substances

Oligodeoxyribonucleotides, Antisense
RNA, Messenger
Vascular Endothelial Growth Factor A
Fusion Proteins, bcr-abl