Physical state changes of membrane lipids in human lung adenocarcinoma A₅₄₉ cells and their resistance to cisplatin

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• 作者：Liang ; Xingjie ; Huang ; Youguo
• 关键词：MDR ; multidrug resistance ; Pgp ; P-glycoprotein ; MC540 ; merocyanine 540 ; NBD-PE ; N-(7-nitro-2 ; 1 ; 3-benzoxadiazol-4-yl)-1 ; 2-hexadecanoyl-Sn-glycero-3-phosphatidyl-ethanolamine ; cisplatin ; cis-dichlorodiammine platinum[II] ; ICP-MS ; inductively coupled plasma
• 刊名：The International Journal of Biochemistry and Cell Biology
• 出版年：2002
• 期刊代码：127_13572725
• 类别：med
• 出版时间：October, 2002
• 卷：34
• 期：10
• 页码：1248-1255
• 文件大小：122 K

摘要

The properties of membrane lipids in sensitive A₅₄₉ and resistant A₅₄₉/DDP cells to cis-dichlorodiammine platinum[II] (cisplatin) were examined by combining different approaches. The results showed that fluorescence intensity (ΔF) of Merocyanine 540 (MC540) was 93.5±21.8 for the sensitive A₅₄₉ cells and 49.5±11.2 for the resistive A₅₄₉/DDP cells, monitored by flow cytometry, which may indicate that membrane lipid packing of the sensitive A₅₄₉ cells were looser than that of the resistant A₅₄₉/DDP cells. Diffusion rate of N-(7-nitro-2,1,3-benzoxadiazol-4-yl)-1,2-hexadecanoyl-Sn-glycero-3-phosphatidyl-ethanolamine (NBD-PE) was slower in A₅₄₉/DDP cells than in A₅₄₉ cells as detected by fluorescence recovery after photobleaching (FRAP) technique. Fatty acid analysis of the membrane lipids showed 21.6, 27.0 and 31.8%increase in the amount of C_18:1, C_18:2 and C_18:3 fatty acid, respectively, in A₅₄₉ cells as compared to A₅₄₉/DDP cells. The total amount of unsaturated fatty acids in the plasma membrane lipid is 69.13%±2.2%for A₅₄₉, and 55.08%±1.8%for A₅₄₉/DDP cells, respectively. The resistance to cisplatin in A₅₄₉/DDP cells was confirmed by the measurements of the transmembrane influx of Rhodamine-123, cisplatin or Bodipy-cisplatin by fluorescence assay and inductively coupled plasma mass spectrometry (ICP-MS). From the results described previously, it is concluded that changes in the membrane lipids “composition” cause a change in the physical state of the plasma membrane lipids and that this may be associated with the resistance of A₅₄₉/DDP cells to cisplatin.