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

Authors

  • Vildan B. Cetintas,

    Corresponding author
    1. Department of Medical Biology, Ege University Faculty of Medicine, Ege University School of Medicine, 35100 Bornova, Izmir, Turkey
      To whom correspondence should be addressed (email vildan.bozok.cetintas@ege.edu.tr).
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  • Ali S. Kucukaslan,

    1. Department of Medical Biology, Ege University Faculty of Medicine, Ege University School of Medicine, 35100 Bornova, Izmir, Turkey
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  • Buket Kosova,

    1. Department of Medical Biology, Ege University Faculty of Medicine, Ege University School of Medicine, 35100 Bornova, Izmir, Turkey
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  • Aslı Tetik,

    1. Department of Medical Biology, Ege University Faculty of Medicine, Ege University School of Medicine, 35100 Bornova, Izmir, Turkey
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  • Nur Selvi,

    1. Department of Medical Biology, Ege University Faculty of Medicine, Ege University School of Medicine, 35100 Bornova, Izmir, Turkey
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  • Gursel Cok,

    1. Department of Thoracic Medicine, Ege University Faculty of Medicine, Ege University School of Medicine, 35100 Bornova, Izmir, Turkey
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  • Cumhur Gunduz,

    1. Department of Medical Biology, Ege University Faculty of Medicine, Ege University School of Medicine, 35100 Bornova, Izmir, Turkey
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  • Zuhal Eroglu

    1. Department of Medical Biology, Ege University Faculty of Medicine, Ege University School of Medicine, 35100 Bornova, Izmir, Turkey
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To whom correspondence should be addressed (email vildan.bozok.cetintas@ege.edu.tr).

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.

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