Association of pregnane X receptor with multidrug resistance-related protein 3 and its role in human colon cancer chemoresistance

H Jiang, K Chen, J He, F Pan, J Li, J Chen… - Journal of …, 2009 - Springer
H Jiang, K Chen, J He, F Pan, J Li, J Chen, W Chen, H Liang
Journal of Gastrointestinal Surgery, 2009Springer
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 …
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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