Growth inhibition of SK-MEL-30 human melanoma cells by antisense c-myc oligonucleotides delivered by poly(N-isopropylacrylamide)/ poly(ethyleneimine) copolymer
| Autor: | E. K. Oskay, Sevil Dinçer, Erhan Pişkin, N. D. Zeybek, A. K. Piskin |
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| Rok vydání: | 2009 |
| Předmět: |
Biomedical Engineering
Acrylic Resins Medicine (miscellaneous) Biomaterials Proto-Oncogene Proteins c-myc chemistry.chemical_compound Cell Line Tumor medicine Humans Polyethyleneimine Particle Size Fibroblast Melanoma Cell Proliferation Drug Carriers Oncogene Cell Death Oligonucleotide Cell growth Temperature hemic and immune systems respiratory system Oligonucleotides Antisense Molecular biology In vitro medicine.anatomical_structure chemistry Cell culture Growth inhibition Intracellular |
| Zdroj: | Journal of tissue engineering and regenerative medicine. 4(4) |
| ISSN: | 1932-7005 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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