Expression of P-gp, MRP, LRP, GST-π and TopoIIα and Acquired Resistance to Cisplatin in Human Lung Adenocarcinoma Cells

Jiarui      Wang; Zhongzhou      He; Lichuan      Zhang; Encheng      Li; Qiang      Meng; Lijuan      Zou; Joseph      Molnar; Qi      Wang

Abstract

This study aimed at analyzing the relationship between the expression of P-gp, MRP, LRP, GST-π and TopoIIα 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-π and TopoIIα 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 TopoIIα 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 TopoIIα in human lung adenocarcinoma cell line A549.

Keywords: Acquired resistance, Cisplatin, GST, LRP, MRP, P-gp, TopoII, Lung cancer, lung adenocarcinoma cell line, immunofluorescence, lung cancer chemotherapy, P-glycoprotein, multidrug-resistance protein, lung resistance-related protein, Glutathione-s-transferase, TopoisomeraseII, glutathione, epipodophyllotoxins, amsacrine, polyclonal antibody, adenocarcinoma cell