PMID- 17721914
OWN - NLM
STAT- MEDLINE
DCOM- 20080506
LR  - 20220311
IS  - 0278-0232 (Print)
IS  - 0278-0232 (Linking)
VI  - 26
IP  - 1
DP  - 2008 Mar
TI  - The association of up-regulation of X-linked inhibitor of apoptosis protein with 
      cell adhesion-mediated drug resistance in U937 cells.
PG  - 21-6
AB  - An increasing body of evidence indicates that environmental factors may 
      contribute to the drug resistance of acute myeloid leukaemia (AML). CAM-DR (cell 
      adhesion-mediated drug resistance) is a reversible, de novo drug resistance 
      induced by adhesion of tumour cell lines to fibronectin (FN). Adhesion was 
      demonstrated to directly regulate the apoptotic machinery. And it was observed in 
      previous studies that high levels of X-linked inhibitor of apoptosis protein 
      (XIAP) were related to resistance to chemotherapeutics in many cancer cell lines. 
      However, whether XIAP is relevant to CAM-DR of AML cells is unknown. In this 
      report, we demonstrated that the mRNA and protein levels of XIAP were increased 
      by 96.15% and 120.92%, respectively in U937 cells cocultured with FN as compared 
      with controls. Antisense oligonucleotides targeting XIAP down-regulated the 
      expression of XIAP and sensitized U937 cells to daunorubicin. In addition, we 
      investigated the signalling pathway involved in the upregulation of XIAP. The 
      levels of phosphorylated Akt (Ser473) were elevated in U937/FN cells and the 
      phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 suppressed XIAP 
      expression and restored the chemosensitivity to daunorubicin. Our findings 
      suggested that adhesion-dependent activation of the PI3K/Akt/XIAP pathway may be 
      one of the factors involved in the CAM-DR of U937 cells. Targeting this pathway 
      may be a useful approach to improve the therapeutic responsiveness of leukaemia 
      cells.
FAU - Wang, Xiaofang
AU  - Wang X
AD  - Department of Hematology, Cancer Hospital of Tianjin, Tianjin Medical University, 
      Tianjin 300060, P.R. China.
FAU - Wang, Chun
AU  - Wang C
FAU - Qin, You-wen
AU  - Qin YW
FAU - Yan, Shi-ke
AU  - Yan SK
FAU - Gao, Yan-rong
AU  - Gao YR
LA  - eng
PT  - Journal Article
PL  - England
TA  - Hematol Oncol
JT  - Hematological oncology
JID - 8307268
RN  - 0 (Fibronectins)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (RNA, Messenger)
RN  - 0 (X-Linked Inhibitor of Apoptosis Protein)
RN  - 0 (XIAP protein, human)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - ZS7284E0ZP (Daunorubicin)
SB  - IM
MH  - *Cell Adhesion
MH  - Daunorubicin/pharmacology
MH  - *Drug Resistance, Neoplasm
MH  - Fibronectins/*physiology
MH  - Humans
MH  - Oligonucleotides, Antisense/pharmacology
MH  - Phosphatidylinositol 3-Kinases/physiology
MH  - Proto-Oncogene Proteins c-akt/physiology
MH  - RNA, Messenger/analysis
MH  - U937 Cells
MH  - Up-Regulation
MH  - X-Linked Inhibitor of Apoptosis Protein/*genetics/physiology
EDAT- 2007/08/28 09:00
MHDA- 2008/05/07 09:00
CRDT- 2007/08/28 09:00
PHST- 2007/08/28 09:00 [pubmed]
PHST- 2008/05/07 09:00 [medline]
PHST- 2007/08/28 09:00 [entrez]
AID - 10.1002/hon.828 [doi]
PST - ppublish
SO  - Hematol Oncol. 2008 Mar;26(1):21-6. doi: 10.1002/hon.828.