Abstract 2769: Expression of p-gp, mrp, lrp, gst-π and topoIIα and intrinsic drug resistance in different lung cancer cell lines

Abstract

Abstract Intrinsic drug resistance is the main reason leading to the failure of chemotherapy in lung cancer. Many drug-resistance related proteins such as P-glycoprotein (P-gp), multidrug-resistance protein (MRP), lung resistance-related protein (LRP), glutathione-s-transferase-π (GST-π) and TopoisomeraseIIα (TopoIIα) are thought to be contributed to the chemoresistance. However, only few studies focus on these five mediators together in intrinsic drug resistance in human lung cancer cell lines. Our study aimed at analyzing the relationship between the basal expression of P-gp, MRP, LRP, GST-π and TopoIIα and intrinsic drug resistance in four different histological types of human lung cancer lines of adenocarcinoma, squamous cell carcinoma, small cell carcinoma and large cell carcinoma (SK-MES-1, SPCA-1, NCI-H-460 and NCI-H-446). The expressions of P-gp, MRP, LRP, GST-π and TopoIIα at protein and mRNA level in the four cell lines were initially detected with immunofluorescence, western blot and RT-PCR. Drug resistance to cisplatin, doxorubicine and VP-16 were determined using MTT through the assay of cell viability. Correlation between the expression of the proteins and resistance to the drugs were analyzed as well. There were positive expressions of the proteins of P-gp, MRP, LRP, GST-π and TOPOIIα in all the four types of cell lines no matter assayed by Western blot or RT-PCR, however, the expression levels were different. Among them, GST-π was the most obviously high, its expression at protein level in SK-MES-1 is more than 3-fold higher compared with that in NCI-H-446, and its expression at mRNA level elevated more than 1.4-fold parallelly. The chemosensitivity to cisplatin, doxorubicine and VP-16 for the four cell lines were different. For cisplatin, its IC50 for SK-MES-1 was the highest compared with other three cell lines with about 2–4-fold elevation; for doxorubicin, its IC50 for SK-MES-1 was the highest as well; but for VP-16, its IC50for SK-MES-1 was the lowest (P<0.05). Pearson correlate analysis indicated that there was a positive correlation between the expression of GST-π and resistance to cisplatin and the expression of TOPOIIα toVP-16 (p<0.05), whereas there was a negative correlation between expression of TOPOIIα and resistance to doxorubicin (p<0.05). In conclusion, the expressions of the chemotherapy resistance related proteins of P-gp, MRP, LRP, GST-π and TOPOIIα in all the four types of human lung cancer cell lines were different. Their different expressions may lead to various chemosensitivity to cisplatin, doxorubicine and VP-16. GST-π was the most important mediator among the five proteins to predict the intrinsic resistance to cisplatin, TOPOIIα also could contribute, to certain degree, to the intrinsic resistance to doxorubicine and VP-16. Further investigation on the mechanism may be necessary for the research of chemotherapy resistance in lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2769.