Expression of MDR1 and MDR3 gene products in paclitaxel-, doxorubicin- and vincristine-resistant cell lines.

Multiple drug resistance is one of the main reasons for low chemotherapeutic efficiency in cancer patients. The proteins that are most frequently implicated to play a role in this mechanism are transmembrane proteins that are members of the ABC family. The most important ABC protein is MDR1 (ABCB1), which is expressed in over fifty percent of drug-resistant cancers. The phosphatidylcholine transporter, MDR3 (ABCB4), exhibits high homology with MDR1. An increasing body of evidence suggests that MDR3 plays a role in drug resistance. In the present study, we used doxorubicin-, paclitaxel- and vincristine-resistant cancer cell lines. A chemosensitivity assay MTT test was performed to assess drug resistance. Quantitative real-time polymerase chain reaction analyses were performed to determine the mRNA expression levels of the MDR1 and MDR3 genes. We observed dose-dependent responses to doxorubicin, paclitaxel and vincristine in the investigated cell lines. In all of the drug-resistant cell lines that we studied, we observed increased MDR1 and MDR3 transcript levels. In a doxorubicin-resistant variant of the LoVo cell line (LoVoDx), MDR3 was expressed at higher levels than MDR1. We also observed high correlations between MDR3 expression and resistance to doxorubicin and paclitaxel. Our results suggest that MDR3 plays an active and important role in drug resistance in the investigated cell lines.