Abstract
Tumor cells that are nonsensitive to anticancer drugs frequently have a multidrug resistant (MDR) phenotype. Many studies with cell lines and patient material have been done to investigate the impact of different resistance markers at protein and mRNA level in drug resistance but with contradictory outcome. In the present study, 26 well-characterised patient-derived non-small cell lung cancer xenografts were used. The known chemosensitivity to etoposide, carboplatin, gemcitabine, paclitaxel and erlotinib was compared to the protein and mRNA expression of BCRP, LRP, MDR1, and MRP1. Further, four of these xenografts were short-term treated to analyse possible regulation mechanisms after therapeutic interventions. We found a borderline correlation between the bcrp mRNA expression and the response of xenografts to etoposide. All other constitutive mRNA and protein expression levels were not correlated to any drug response and were not significantly influenced by a short term treatment. The present results indicate that the expression levels of MDR proteins and mRNA investigated do not play an important role in the chemoresistance of NSCLC in the in vivo situation.
Highlights
Lung cancer is still one of the most frequent cancers with about 1 million incidences worldwide each year
The present results indicate that the expression levels of multidrug resistant (MDR) proteins and mRNA investigated do not play an important role in the chemoresistance of NSCLC in the in vivo situation
It was shown that amplification and overexpression of BCRP emerged as the dominant resistance mechanism in MDR1 and MRP1-deficient mouse fibroblast and kidney cell lines that were selected for resistance to etoposide [13]
Summary
Lung cancer is still one of the most frequent cancers with about 1 million incidences worldwide each year. Three human ABC transporters are primarily associated with the multidrug resistance, namely, P-glycoprotein (P-gp, MDR1, ABCB1), multidrug resistance protein 1 (MRP1, ABCC1), and breast cancer resistance protein (BCRP, ABCG2). They have broad and, to a certain extent, overlapping substrate specificities and are involved in transport processes for a variety of drugs used in chemotherapy. We wanted to address the question if the level of resistance markers on mRNA or protein level is correlated with the response of xenografts to classical cytotoxic drugs (etoposide, carboplatin, gemcitabine, and paclitaxel) or targeted therapy (erlotinib)
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