title: Association of pregnane X receptor with multidrug resistance-related protein 3 and its role in human colon cancer chemoresistance.
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.
authors: Department of Oncology, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Main Street, Shapingba District, Chongqing, 400038, China. jiangtingfu@163.com
authors: Heng
authors: H
authors: Jiang
authors: Keli
authors: K
authors: Chen
authors: Jianming
authors: J
authors: He
authors: Feng
authors: F
authors: Pan
authors: Jianjun
authors: J
authors: Li
authors: Jianfang
authors: J
authors: Chen
authors: Wensheng
authors: W
authors: Chen
authors: Houjie
authors: H
authors: Liang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D018432:Drug Resistance, Multiple / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D006801:Humans; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000378:metabolism*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; C095122:multidrug resistance protein 3