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Archive > Volume 20 Issue 4 > 2013,20(4):391-397. DOI:10.3872/j.issn.1007-385X.2013.04.002 Prev Next
Prompt Report
Targeting cytotoxicity effect of IL-3-lidamycin fusion protein on CD123+ leukemia cells
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Abstract:
Objective: To construct a fusion protein IL-3-lidamycin(IL-3-LDM) with an IL-3 guide and a LDM warhead, and to investigate its targeting cytotoxicity on CD123+ leukemia cells in vivo. Methods: IL-3-LDP (interlekin 3-lidamycin) fusion protein was obtained in a prokaryotic system, and further assembled with active enediyne (AE) to get IL-3-LDM. The expression of CD123 in six leukemia cell lines (KG1-a, TF-1, M07e, HL-60, K562, Raji) was detected by flow cytometry and the binding ability of IL-3-LDM with different leukemia cell lines was examined. The cytotoxicity of IL-3-LDM fusion protein on leukemia cells with different CD123 expression levels was detected by CCK-8. Results: The purity of recombinant protein IL-3-LDM was more than 90% after assembling with AE. The results showed that the CD123 expression ratio was 88.9% on AML (acute myeloid leukemia) KG-1a cells, ＞75% on MO7e and TF-1 cells, 7.8% on HL-60 cells, and negative on K562 and Raji cells. The expression ratio of CD123 on leukemia cells （KG-1a, MO7e, TF-1 and HL-60）was positively related to its binding ability and sensitivity to IL-3-LDM in vitro. The cytotoxicity of LDM on KG-1a cells which expressed the highest level of CD133 was 1 415.8 fold stronger than that of adriamjcin (ADR), and the cytotoxicity of IL-3-LDM was 9.6 fold than that of LDM. Conclusion: IL-3-LDM fusion protein can effectively target cytotoxic drug LDM to kill CD123+ leukemia cells.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No. 30971291), and the Science and Technology Development Plan of Tianjin (No. 05YFGZGX02800)
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