Department of Medical Biology, Ege University Faculty of Medicine, Ege University School of Medicine, Bornova, Izmir, Turkey.
Cell Biol Int. 2012 Mar 1;36(3):261-5. doi: 10.1042/CBI20110329.
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.
我们研究了可能导致耐药性产生的凋亡缺陷步骤。为此，用顺铂处理 A549 和 Calu1 NSCLC（非小细胞肺癌）细胞系以获得耐药亚系。确定了每个细胞系的基因表达谱和 BAD（Bcl-2/Bcl-XL 拮抗剂，导致细胞死亡）蛋白的磷酸化状态。用适当的顺铂剂量处理细胞系后，分析细胞死亡和细胞色素 c 释放。耐药细胞系中 BAD、Bid、半胱天冬酶 4 和 6 的基因表达明显降低，BAD 的差异磷酸化状态似乎也在顺铂耐药性的发展中起作用。由于这是一种新的顺铂耐药 Calu1 细胞系，值得注意的是，在 CR-Calu1 细胞系中，DNA 片段化、凋亡细胞比例和细胞色素 c 水平降低最为明显。
