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Journal of Gastrointestinal Surgery

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01-10-2009 | Original Article

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

Authors: Heng Jiang, Keli Chen, Jianming He, Feng Pan, Jianjun Li, Jianfang Chen, Wensheng Chen, Houjie Liang

Published in: Journal of Gastrointestinal Surgery | Issue 10/2009

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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Title: Association of Pregnane X Receptor with Multidrug Resistance-Related Protein 3 and its Role in Human Colon Cancer Chemoresistance
Authors: Heng Jiang
Keli Chen
Jianming He
Feng Pan
Jianjun Li
Jianfang Chen
Wensheng Chen
Houjie Liang
Publication date: 01-10-2009
Publisher: Springer-Verlag
Published in: Journal of Gastrointestinal Surgery / Issue 10/2009
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-009-0964-x

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Background

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Results

Conclusions

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