title: The mechanism of the G0/G1 cell cycle phase arrest induced by activation of PXR in human cells.
abstract: BACKGROUND
  Pregnane X receptor (PXR) is an important transcriptional regulator that plays important roles in the cell metabolism and cell growth by regulating the transcriptional of a sort of metabolizing enzymes.
  
  
  OBJECTIVE
  To investigate whether rifampicin effected HepG2 cells growth and the inhibition was due to the G0/G1 phase arrest.
  
  
  METHODS
  PXR-knockdown experiments using RNAi showed that the cell cycle phase arrest mediated by rifampicin based on activation of PXR. The results also indicated that cell phase arrest by rifampicin could protect cells form UVB-induced DNA damage. Retinoid X receptor alpha (RXRα) expression level in cells is another key factor for cell cycle phase arrest mediated by rifampicin. Both over expression and lacking expression of RXRα in cell reduced the cell arrest efficiency mediated by rifampicin. In the study, we found that rifampicin inhibited HepG2 cells growth and demonstrated that the inhibition is due to the G0/G1 phase arrest through flow cytometry analysis.
  
  
  CONCLUSIONS
  The results showed that RXRα promote cell cycle phase transition rate of HepG2. Competitive bind of rifampicin-activated PXR with RXRα is one main reason to arrest cell cycle phase through inhibiting combination of RXRα with other partners. Rifampicin could promote cell growth rate when RXRα expressed more excessively than PXR in cells.
authors: Department of Bioengineering, College of Biological Science and Biotechnology, Fuzhou University, Fuzhou, 350002 Fujian, China.
authors: Weiliang
authors: W
authors: Zhuang
authors: Zhenhua
authors: Z
authors: Jia
authors: Huahua
authors: H
authors: Feng
authors: Jun
authors: J
authors: Chen
authors: Hang
authors: H
authors: Wang
authors: Yanghao
authors: Y
authors: Guo
authors: Chun
authors: C
authors: Meng
mesh_terms: D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D016193:G1 Phase / Q000187:drug effects*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D056945:Hep G2 Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology; D000077297:Pregnane X Receptor; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D011987:Receptors, Steroid / Q000187:drug effects*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016192:Resting Phase, Cell Cycle / Q000187:drug effects*; D047490:Retinoid X Receptor alpha / Q000235:genetics / Q000378:metabolism; D012293:Rifampin / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D000077297:Pregnane X Receptor; D034741:RNA, Small Interfering; D011987:Receptors, Steroid; D011993:Recombinant Fusion Proteins; D047490:Retinoid X Receptor alpha; D012293:Rifampin