Growth inhibition of SK-MEL-30 human melanoma cells by antisense c-myc oligonucleotides delivered by poly(N-isopropylacrylamide)/ poly(ethyleneimine) copolymer.

Abstract

The c-myc oncogene has been shown to be overexpressed in a number of malignancies and plays a key role in the abnormal growth regulation of melanoma cells. This study aimed to provide an efficient system for the in vitro manipulation of c-myc expression by antisense oligonucleotides. Therefore, we used poly(NIPA)/PEI2B copolymer as vector in order to improve the intracellular availability and stability of AS ODNs. We targeted oligonucleotide sequences within the human c-myc mRNA as free AS ODNs or conjugated with a thermosensitive copolymer, in an effort to inhibit the growth of human melanoma cells. The conjugates adopted more positive charge and smaller size at 37 degrees C and they had no toxic effects on human fibroblast cells. The conjugated AS ODNs showed increased antiproliferative effect on melanoma cells as compared to free AS ODNs. At a concentration of 100 ng, AS ODNs inhibited SK-MEL 30 human melanoma cell line proliferation maximally by 18.6%, whereas the same amount of conjugated AS ODN provided 52% inhibition. The greatest inhibition was obtained by conjugates having a polymer:AS ODN ratio of 9. Greatest inhibition was detected at 48 h and decreased after 96 h, which may be due to the depletion of AS ODNs. The results confirm the enhanced antiproliferative effects of poly(NIPA)/PEI2B-conjugated AS ODNs, which may provide improved intracellular availability for c-myc-directed antisense strategies.

• Authors: S Dinçer, E K Oskay, A K Piskin, N D Zeybek, E Pişkin
• Journal: Journal of tissue engineering and regenerative medicine (J Tissue Eng Regen Med) Vol. 4 Issue 4 Pg. 284-90 (Jun 2010) ISSN: 1932-7005 [Electronic] England
• PMID: 19967748 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 John Wiley & Sons, Ltd.

Chemical References

• Acrylic Resins
• Drug Carriers
• Oligonucleotides, Antisense
• Proto-Oncogene Proteins c-myc
• poly(N-isopropylacrylamide)-poly(ethyleneimine) copolymer
• Polyethyleneimine

Topics

• Acrylic Resins
• Cell Death (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Carriers
• Humans
• Melanoma (genetics, metabolism, pathology, therapy)
• Oligonucleotides, Antisense (pharmacology)
• Particle Size
• Polyethyleneimine (analogs & derivatives)
• Proto-Oncogene Proteins c-myc (biosynthesis, genetics)
• Temperature