Evaluation of drug transporters' significance for multidrug resistance in head and neck squamous cell carcinoma.

Abstract

Multidrug resistance (MDR) hampers chemotherapy in head and neck squamous cell carcinoma (HNSCC). There is little information about MDR mediating drug transporters in HNSCC. Nine HNSCC cell lines were characterized concerning drug transporter expression and susceptibility to cisplatin, paclitaxel, and 5-fluorouracil (5-FU) using a DNA microarray and proliferation assays. Three cells lines were precisely investigated for transporter expression using reverse transcriptase-polymerase chain reaction (RT-PCR) and drug resistance before and after simulated chemotherapies. The cell lines differed in drug resistance and transporter expression. Cisplatin and paclitaxel resistances were inversely associated. Drugs rendered HNSCC cells resistant, cross-resistant, or cross-sensitive. Sensitivity changes were accompanied by transporter mRNA expression changes. Paclitaxel was identified as a potent inducer of numerous drug transporters and phenotypic MDR in HNSCC. Thus, cytostatic susceptibility of HNSCC cannot exclusively be deduced from the expression of single transporters but more likely of the entire transportome and non-transporter modulators.