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Association of Pregnane X Receptor with Multidrug Resistance-Related Protein 3 and its Role in Human Colon Cancer Chemoresistance

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Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

Pregnane xenobiotic receptor (PXR), a ligand-activated transcription factor, regulates the drug metabolism and transport. Its activation can reduce the efficacy of antineoplastic agents. The aim of this study was to investigate the role of PXR and the relationship between PXR and multidrug resistance-related protein 3 (MRP3) in human colon cancer chemoresistance.

Results

The results showed that both the mitochondrial RNA (mRNA) and protein levels of PXR and MRP3 were much higher in colon cancer tissues than that in nonneoplastic tissues by reverse transcriptase polymerase chain reaction and Western blot analysis. MRP3 mRNA was significantly correlated with PXR mRNA in cancerous (P = 0.001) and nonneoplastic (P < 0.001) colon tissues with Pearson correlation test. The expressions of PXR, SP1, and MRP3 were markedly enhanced after rifampicin treatment. On the other hand, the protein level of MRP3 decreased after stable RNA interference of PXR. It also observed that PXR, activated by rifampicin or knocked down via short hairpin RNAs, could enhance or reduce cells resistance to the chemotherapeutic agents through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.

Conclusions

The results suggested that PXR, associated with MRP3, may play an important role in human colon cancer resistance to chemotherapeutics and SP1 may be involved in the induction of MRP3 by PXR activation.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (grant no. 30570842). We thank Dr. Yingxue Hao for his generous help in collecting up patients and Mr. Wen Qin for his excellent writing assistance.

Competing interests

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Oncology, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Main Street, Shapingba District, Chongqing, 400038, China

    Heng Jiang, Keli Chen, Jianming He, Feng Pan, Jianjun Li, Jianfang Chen & Houjie Liang

  2. Department of Gastroenterology, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Main Street, Shapingba District, Chongqing, 400038, China

    Wensheng Chen

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  1. Heng Jiang
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  2. Keli Chen
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Correspondence to Wensheng Chen or Houjie Liang.

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Jiang, H., Chen, K., He, J. et al. Association of Pregnane X Receptor with Multidrug Resistance-Related Protein 3 and its Role in Human Colon Cancer Chemoresistance. J Gastrointest Surg 13, 1831–1838 (2009). https://doi.org/10.1007/s11605-009-0964-x

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  • DOI: https://doi.org/10.1007/s11605-009-0964-x

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