Expression of P-gp, MRP, LRP, GST-π and Topoiiα and acquired resistance to cisplatin in human lung adenocarcinoma cells

LETTERS IN DRUG DESIGN & DISCOVERY(2011)

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摘要
This study aimed at analyzing the relationship between the expression of P-gp, MRP, LRP, GST-pi and TopoII alpha and acquired resistance to cisplatin in lung adenocarcinoma cell line A549. Drug resistance to cisplatin was determined using MTT assays. The expressions of P-gp, MRP, LRP, GST-pi and TopoII alpha were measured by immunofluorescence, Western blot and RT-PCR. The results showed that there was a significant elevation of IC50 of cisplatin in A549/DDP cells compared to A549 cells (73.95 +/- 7.26 versus 7.28 +/- 0.74). The expression of P-gp and MRP in A549/DDP cells was approximately 1.5-fold higher than that in A549 cells (61.99 +/- 2.63 versus 43.52 +/- 1.22; 34.11 +/- 2.17 versus 22.80 +/- 2.31 respectively), whereas TopoII alpha expression was about 3-fold lower in A549/DDP cells than that in A549 cells (0.34 +/- 0.06 versus 0.92 +/- 0.03). In conclusion, acquired resistance to cisplatin was associated with the up-regulation of P-gp and MRP and the down-regulation of TopoII alpha in human lung adenocarcinoma cell line A549.
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关键词
Acquired resistance,Cisplatin,GST-pi,LRP,MRP,P-gp,TopoII alpha,Lung cancer
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