The expression and significance of MRP1, LRP, TOPOIIβ, and BCL2 in tongue squamous cell carcinoma

Abstract

Multiple drug resistance protein 1 (MRP1), lung resistance protein (LRP), topoisomerase IIβ (TOPOIIβ) and B-cell lymphoma 2 (BCL2) are well known in the development of drug resistance in cancer cells. The aim of this study was to evaluate the relationship between them and the clinicopathological features, their expression differences between tumor tissue and experimental drug-resistant model in tongue carcinoma. Multiple drug resistance protein 1, LRP, TOPOIIβ, and BCL2 expression was examined by immunohistochemistry in specimens from radical surgeries of 65 patients with tongue carcinoma. A cisplatin-resistance cell line, SCC-15/cisplatin, was established from a cisplatin-sensitive cell line, SCC-15. A MTT-based method was used to analyze drug potencies. Immunofluorescence was used to detect protein expression in both cell lines. Western blot was used to compare the protein expressions in specimens and SCC-15/cisplatin cells. We found higher expression of MRP1, LRP, and BCL2 and lower expression of TOPOIIβ in tongue carcinoma compared with adjacent non-neoplastic tongue tissues (P < 0.05). In addition, MRP1 and TopoIIβ expression were significantly associated with clinical stage, lymph node metastasis and histologic grade, and LRP was significantly associated with histologic grade in the samples (P < 0.05). Finally, Western blot showed that higher expressions of MRP1, LRP, and BCL2 and lower expression of TopoIIβ were observed in SCC-15/cisplatin cells than in clinical samples. Our results suggest that the high expressions of MRP1, LRP, and BCL2 and low expression of TOPOIIβ in patients with tongue carcinoma indicates that intrinsic drug resistance may exist in tongue carcinoma, and is associated with tumor differentiation and cisplatin resistance in tongue carcinoma.