Analysis of multidrug resistance-associated protein (MRP) gene and chemosensitivity testing in non small cell lung cancer (NSCLC) patients

The occurrence of multidrug resistance (MDR) is a primary factor of the dif ficulty in achieving better results in Non Small Cell Lung Cancer (NSCLC) c hemotherapy. Detecting MDR of tumor before chemotherapy will possess refere nce value in choosing effective chemotherapy regimens. Overexpression of mu ltidrug resistance-associated protein (MRP) gene has been found and proved to be related to MDR in NSCLC. in the present study, 32 NSCLC samples were examined the expression of MRP gene and chemosensitivity to 9 antitumor age nts by reverse transcription-polymerase chain reaction (RT-PCR), immunohist ochemical analysis and in vitro chemosensitivity assay. The positive expres sion rate of MRP mRNA in NSCLC was 72%. The overexpression rate of MRP in N SCLC was 66%, but no positive expression in adjacent normal lung tissue. Po sitive staining of MRP was located in the plasma membrane and the cytoplasm of tumor cells. MRP mRNA and MRP expression of adenocarcinoma was higher t han that of squamous carcinoma, but no significant difference was found. MR P mRNA and MRP expression of moderate differentiation carcinoma was signifi cantly higher than that of poor differentiation carcinoma (P<0.05). The exp ressions of MRP gene did not appeared to be related to tumor stages and lym ph node metastasis in NSCLC. The chemosensitivity rate of 32 NSCLC samples to 9 antitumor agents was as follows: Navelbine 78%, Vincristine 75%, Mitom ycin C 69%, Cisplatin 63%, Carboplatin 63%, Etoposide 56%, Adriamycin 53%, Methotrexate 22%, 5-Fluorouracil 19%. The expression rate of MRP in NSCLC, which was resistant to Vincristine, Etoposide and Adriamycin, was higher th an that which was sensitive to these drugs (P<0.05). The results indicate t hat MRP gene was an important mechanism of intrinsic drug resistance in NSC LC, overexpression of MRP gene could be achieved by the regulation of trans criptional and translational level. There was a guiding significance in det ecting MRP gene and in vitro chemosensitivity assay for specific chemothera py in NSCLC.