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Updated: Jun 22, 2026
High-throughput Fluorometric Measurement of Potential Soil Extracellular Enzyme Activities
Published on: November 15, 2013
[Not Available]
Jana Rolff1, Cornelia Dorn, Johannes Merk
1Experimental Pharmacology & Oncology GmbH, Robert-Rössle-Street 10, 13122 Berlin, Germany.
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.
Insights
Multidrug resistance (MDR) in non-small cell lung cancer (NSCLC) is not strongly linked to common resistance markers. Protein and mRNA levels of MDR markers showed little correlation with drug response in patient-derived xenografts.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Multidrug resistance (MDR) is a significant challenge in non-small cell lung cancer (NSCLC) treatment.
- Previous studies on MDR markers in NSCLC have yielded conflicting results regarding their impact on chemosensitivity.
Purpose of the Study:
- To investigate the correlation between MDR-related protein and mRNA expression and chemosensitivity in patient-derived NSCLC xenografts.
- To analyze potential regulatory mechanisms of MDR markers following therapeutic interventions.
Main Methods:
- Utilized 26 well-characterized patient-derived NSCLC xenografts.
- Assessed chemosensitivity to etoposide, carboplatin, gemcitabine, paclitaxel, and erlotinib.
- Quantified protein and mRNA expression of BCRP, LRP, MDR1, and MRP1.
- Performed short-term treatment on four xenografts to study regulatory mechanisms.
Main Results:
- A borderline correlation was observed between BCRP mRNA expression and etoposide response.
- No significant correlation was found between constitutive mRNA/protein levels of investigated MDR markers and drug response.
- Short-term therapeutic interventions did not significantly influence the expression levels of these MDR markers.
Conclusions:
- The expression levels of investigated MDR proteins and mRNA do not appear to play a major role in the in vivo chemoresistance of NSCLC.
- These findings suggest that other mechanisms may be more critical in conferring drug resistance in NSCLC.
