Cisplatin resistance induced by decreased apoptotic activity in non-small-cell lung cancer cell lines


CETINTAS V. , KUCUKASLAN A. S. , KOSOVA B. , TETIK A. , SELVİ N., ÇOK G. , ...More

CELL BIOLOGY INTERNATIONAL, vol.36, no.3, pp.261-265, 2012 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 36 Issue: 3
  • Publication Date: 2012
  • Doi Number: 10.1042/cbi20110329
  • Title of Journal : CELL BIOLOGY INTERNATIONAL
  • Page Numbers: pp.261-265
  • Keywords: apoptosis, Bcl-2/Bcl-X(L)antagonist, causing cell death (BAD) phosphorylation, cisplatin resistance, cytochrome c release, ESTABLISHMENT

Abstract

We have investigated defective steps in apoptosis that might account for the development of resistance. For this purpose, A549 and Calu1 NSCLC (non-small-cell lung cancer) cell lines were treated with cisplatin to obtain resistant sub-lines. Gene expression profiles and the phosphorylation status of the BAD (Bcl-2/Bcl-X-L-antagonist, causing cell death) protein were determined for each cell line. Cell death and cytochrome c release were analysed after treating cell lines with their appropriate cisplatin doses. Gene expression of BAD, Bid, caspases 4 and 6 were clearly decreased in the resistant cell lines, and the differential phosphorylation status of BAD also seemed to play a role in the development of cisplatin resistance. Since this is a new cisplatin-resistant Calu1 cell line, it is noteworthy that DNA fragmentation, apoptotic cell ratio and cytochrome c levels were most decreased in the CR-Calu1 cell line.