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Increased expression and function of P-glycoprotein in peripheral blood CD56+ cells is associated with the chemoresistance of non-small-cell lung cancer

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Abstract

Purpose

Chemoresistance is common among non-small-cell lung cancer (NSCLC), P-glycoprotein (P-gp), encoded by the human multi-drug-resistant MDR1 gene, and multidrug-resistance protein 1 (MRP1) might be major contributors. The aim of the present study was to develop an effective method to investigate the expression and function of P-gp in the peripheral CD56+ cells in order to clarify their correlation with the chemoresistance in NSCLC.

Methods

Using microbead technology and a RT-qPCR methodology, we evaluated the expression levels of P-gp and MRP1 in the purified CD56+ cells in the chemoresistance and chemo-naive NSCLC patients compared with that in the healthy volunteers. Flow cytometric analysis was used to investigate the changes of P-gp function in the CD56+ cells between the three cohorts.

Results

The MDR1 gene expression was elevated markedly (twofold–tenfold), and P-gp function was increased in the chemoresistance cohort compared with the chemo-naive and the healthy cohorts; whereas there was only about two times averagely elevated for the MRP1 gene expression. No statistical significance (p > 0.05) was seen with respect to the expression of MDR1 and MRP1, the function of P-gp between the chemo-naive and the healthy cohorts.

Conclusions

P-gp in peripheral CD56+ cells demonstrated possible clinical relevance as predictive biomarkers for the identification of chemoresistance in NSCLC, while MRP1 may not play a significant role in the drug resistance in NSCLC. The potential applications for this finding are provided evidence to screen the potential P-gp reversors and to diagnose and manage the chemoresistance in NSCLC patients.

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Acknowledgments

The authors wish to thank the participating patients, volunteers, and their families, and the clinical doctors. This study was supported by grants from social welfare projects for scientific research of Henan Province, China.

Conflict of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Zhengzhou University, Zhenzhou, 45001, Henan, China

    Li Han & Ya Feng Wang

  2. Henan Key Laboratory for Pharmacology of Liver Diseases, Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, 40 Daxue Road, Zhengzhou, 450052, Henan, China

    Li Han, Yan Zhang, Ning Wang, Su Na Liu, Jin Hua Jiang & Qing Duan Wang

  3. The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Qing Xia Fan

  4. Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China

    Jing Ke Yang & Ke Li

  5. Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, Nanyang, China

    Xiao Juan Guo

  6. The First Affiliated Hospital of Henan College of Traditional Chinese Medicine, Zhengzhou, China

    Kui Peng Wang

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  1. Li Han
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  2. Ya Feng Wang
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  3. Yan Zhang
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  10. Ke Li
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  11. Jin Hua Jiang
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Corresponding author

Correspondence to Qing Duan Wang.

Additional information

Li Han and Ya Feng Wang contributed equally to this work.

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Han, L., Wang, Y.F., Zhang, Y. et al. Increased expression and function of P-glycoprotein in peripheral blood CD56+ cells is associated with the chemoresistance of non-small-cell lung cancer. Cancer Chemother Pharmacol 70, 365–372 (2012). https://doi.org/10.1007/s00280-012-1915-x

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  • DOI: https://doi.org/10.1007/s00280-012-1915-x

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