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


Dincer S. , Oskay E. K. , Piskin A. K. , ZEYBEK N., Piskin E.

JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, cilt.4, ss.284-290, 2010 (SCI İndekslerine Giren Dergi) identifier identifier

  • Cilt numarası: 4 Konu: 4
  • Basım Tarihi: 2010
  • Doi Numarası: 10.1002/term.239
  • Dergi Adı: JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
  • Sayfa Sayıları: ss.284-290

Özet

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-MEI, 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. Copyright (C) 2009 John Wiley & Sons, Ltd.