title: Cisplatin resistance induced by decreased apoptotic activity in non-small-cell lung cancer cell lines.
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-XL-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.
authors.affiliation: Department of Medical Biology, Ege University Faculty of Medicine, Ege University School of Medicine, Bornova, Izmir, Turkey. vildan.bozok.cetintas@ege.edu.tr
authors.forename: Vildan B
authors.initials: VB
authors.lastname: Cetintas
authors.forename: Ali S
authors.initials: AS
authors.lastname: Kucukaslan
authors.forename: Buket
authors.initials: B
authors.lastname: Kosova
authors.forename: Aslı
authors.initials: A
authors.lastname: Tetik
authors.forename: Nur
authors.initials: N
authors.lastname: Selvi
authors.forename: Gursel
authors.initials: G
authors.lastname: Cok
authors.forename: Cumhur
authors.initials: C
authors.lastname: Gunduz
authors.forename: Zuhal
authors.initials: Z
authors.lastname: Eroglu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D053938:DNA Fragmentation; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin