SEQUENTIAL OVEREXPRESSION OF LRP AND MRP BUT NOT P-GP170 IN VP16-SELECTED A549 ADENOCARCINOMA CELLS

Chemoresistance remains the major obstacle to successful therapy of lu ng cancer. In order to understand drug resistance mechanisms, the expr ession of three proteins involved in multidrug resistance (P-gp, MRP a nd LRP) was studied, using the non-small cell lung cancer (NSCLC) A549 cell line. In addition, 3 levels of resistance were obtained by conti nuous exposure of cells to etoposide (VP16), which led to a 22-fold in crease of the resistance index. The wild-type A549 strongly expressed the LRP protein while MRP protein was found at a moderate level. Induc tion of resistance paralleled an increase of the expression of the mrp gene and a decrease of the lrp gene; the mdr1 gene was not expressed. Taken together, these results indicate that intrinsically resistant N SCLC cells exhibit a complex pattern of MDR proteins, still susceptibl e to evolve under treatment. Such a fact would have to be considered i n clinical situations.