Table 2.
Background on PXR/SXR research | Materials and methods | Results and discussion | Ref. |
PXR can enhance detoxification of irinotecan in cancer cells | PXR cDNA-mediated expression in human colorectal cancer cell lines Human liver and colon biopsies |
PXR cDNA-mediated overexpression led cell-resistance to irinotecan and SN38 | Raynal et al.[25] |
PXR/SXR is known to be involved in the upregulation of genes associated with the detoxification of irinotecan | ChIP with anti-PXR/SXR antibodies. PXR/SXR mediated induction of CYPs and ABC transporters after exposure of LS180 and HepG2 cells to irinotecan or SN-38 | PXR enrichment induced by SN-38 treatment to CYP3A4 gene enhancer and promoter regions SN-38 induced CYP3A4/5 (6-13-fold) and UGT1A1 and MRP2 by 2-3-fold. PXR/SXR decreased irinotecan cytotoxicity in LS180 |
Basseville et al.[26] |
ChIP: Chromatin-immunoprecipitation; PXR: pregnane X receptor; SXR: steroid and xenobiotic receptor; CYPs: cytochrome P-450; ABC: ATP-binding cassette.