Table 1.
Drugs | PXR | PXR target genes | Chemotherapeutic effects | Models | References |
---|---|---|---|---|---|
Irinotecan | Expression ↑ by transfection | UGT1A1 ↑ UGT1A9 ↑ UGT1A10 ↑ CYP3A4 ↑ | Metabolism ↑ Sensitivity ↓ |
LS174T cells, HCT116 cells | [64, 65] |
Expression ↓ by shRNA and siRNA | UGT1A1 ↓ | Metabolism ↓ Sensitivity ↑ |
LS174T cells, HCT116 cells | [64] | |
Activation by rifampicin and SN-38 | UGT ↑ CYP3A4 ↑ CYP3A5 ↑ MRP2 ↑ P-gp ↑ | Metabohsm ↑ Efflux ↓ |
Mice, LS180 cells, HePG2 cells, HCT116 cells | [18, 24, 65, 66, 68] | |
Tamoxifen | Expression ↑ by transfection | Ki-67 ↑ ABCC2 ↑ OATP1A2 ↑ | Drug resistance ↑ | MCF-7 cells, TAMR-MCF-7 cells | [19, 73] |
Expression ↓ by shRNA | Sensitivity ↑ | MDA-MB-231 cells, MCF-7 cells | [74, 75] | ||
Activation by TAM,4-OH-TAM, SR12813, rifampicin, anandamide and clotrimazole | CYP3A4 ↑ MDR1 ↑ MRP2 ↑ OATP1A2 ↑ | Metabolism ↑ Efflux ↑ Drug resistance ↑ |
MCF-7 cells, T-47D cells, ZR-75-1 cells, MCF-7 cells | [73-79] | |
BAX ↑ P21 ↑ | Apoptosis ↑ | MCF-7 cells, ZR-75-1 cells | [50] | ||
Inhibition by A-792611 | OATPlA2↓ | Sensitivity ↑ | T47-D cells | [75] | |
Paclitaxel | Expression↓ by siRNA and shRNA | CYP3A4 ↓ MDR1 ↓ | Apoptosis ↑ Proliferation ↓ | HEC-1 cells, MDA-MB-231 cells | [22, 74, 86] |
Activation by paclitaxel, SR12813, rifampicin | CYP3A ↑ CYP2B6 ↑ CYP2C8 ↑ MDR1 ↑ | Metabolism ↑ Efflux ↑ Apoptosis ↓ Proliferation ↑ |
HEC-1 cells, PC-3 cells, MDA-MB-231 cells, SKOV-3 cells | [24, 74, 86-89] | |
Doxorubicin | Avtivation by rifampicin and VP-PXR | BAG3 ↓ BIRC2 ↓ MCL-1 ↓ BAK1 ↓ TP53/p53 ↓ P-gp ↑ | Apoptosis ↓ Sensitivity ↓ |
HCT116 cells, LS180 cells | [52, 77] |
Inhibition by ecteinascidin-743 | P-gP↓ | Sensitivity ↑ | Osteosarcoma cells | [94] | |
PXR polymorphisms | Patients harboring PXR*1B showed higher CYP3A4 levels compared with PXR*lA and PXR*lC | Patients harboring PXR*1B showed higher drug clearance compared with PXR*lA and PXR*lC | Patients | [95] | |
Vinblastine | Activation by SR12813 and vinblastine | ABCC2 ↑ ABCC3 ↑ CYP3A4 ↑ | Sensitivity ↓ | PC-3 cells, LS174T cells, Patients | [86, 101, 102] |
Expression↓ by siRNA | MDR1 ↑ CYP3A4 ↑ | Sensitivity ↑ | MCF-7 cells, MDA-MB-231 cells | [74] | |
ATRA | Activation by PCN, Rifampin and dexamethasone | CYP3A ↑ CYP26 ↑ MDR1 ↑ ABCC3 ↑ OATP ↑ | AUC ↓ Sensitivity ↓ |
Mice | [109] |
CPA&IFO | Activation by rifampin and dexamethasone | CYP3A4 ↑ CYP2C8 ↑ CYP2C9 ↑ | Metabolism ↑ Sensitivity ↑ |
Primary cultures hepatocytes | [114] |