PMID- 17953712
OWN - NLM
STAT- MEDLINE
DCOM- 20080215
LR  - 20220331
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Linking)
VI  - 99
IP  - 1
DP  - 2008 Jan
TI  - Hypoxia-inducible factor-1 alpha contributes to hypoxia-induced chemoresistance 
      in gastric cancer.
PG  - 121-8
AB  - Hypoxia induced drug resistance is a major obstacle in the development of 
      effective cancer therapy. Our previous study revealed that hypoxia-inducible 
      factor-1 (HIF-1), the major transcriptional factor significantly activated by 
      hypoxia, was overexpressed in gastric vincristine-resistant cells 
      SGC7901/vincristine (VCR) under normoxic conditions, which suggested that it was 
      associated with drug resistance in gastric cancer cells. In the present study, a 
      colony-forming assay revealed that hypoxia and forced HIF-1 alpha expression 
      increased maximal -8.9-fold or -14.8-fold of IC(50) toward vincristine in gastric 
      cancer cell lines SGC7901 and SGC7901/VCR, respectively (P < 0.01). 
      Annexin-V/propidium iodide staining analysis revealed hypoxia or forced HIF-1 
      alpha expression reduced apoptosis by 24% or 18% in SGC7901 cells (P < 0.05). 
      Flow cytometry analysis of intracellular adriamycin revealed that hypoxia and 
      forced expression of HIF-1 alpha increased -1.79-fold or -2.36-fold of the 
      adriamycin releasing index, respectively (P < 0.05). However, resistance 
      acquisition subject to hypoxia in vitro and in vivo was suppressed by blocking 
      HIF-1 alpha expression with siRNA. We further demonstrated that HIF-1 alpha 
      overexpression showed a 1.85-fold increased expression of Bcl-2 and a 2.16-fold 
      decreased expression of Bax, and also showed significantly induced expression of 
      p-gp and MRP1, which indicated that HIF-1 alpha may confer hypoxia-induced drug 
      resistance via inhibition of drug-induced apoptosis and decreases in 
      intracellular drug accumulation.
FAU - Liu, Lili
AU  - Liu L
AD  - State Key Laboratory of Cancer Biology, Institute of Digestive Diseases, Xijing 
      Hospital, Fourth Military Medical University, 15 Changle West Road, Xi'an 710032, 
      China.
FAU - Ning, Xiaoxuan
AU  - Ning X
FAU - Sun, Li
AU  - Sun L
FAU - Zhang, Hongbo
AU  - Zhang H
FAU - Shi, Yongquan
AU  - Shi Y
FAU - Guo, Changcun
AU  - Guo C
FAU - Han, Shuang
AU  - Han S
FAU - Liu, Jie
AU  - Liu J
FAU - Sun, Shiren
AU  - Sun S
FAU - Han, Zheyi
AU  - Han Z
FAU - Wu, Kaichun
AU  - Wu K
FAU - Fan, Daiming
AU  - Fan D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071022
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (BAX protein, human)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 5J49Q6B70F (Vincristine)
RN  - Y49M64GZ4Q (multidrug resistance-associated protein 1)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 
      1/biosynthesis/genetics/metabolism
MH  - Apoptosis/drug effects
MH  - Cell Hypoxia/physiology
MH  - Cell Line, Tumor
MH  - Drug Resistance, Neoplasm
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis/genetics/*metabolism
MH  - Multidrug Resistance-Associated Proteins/biosynthesis/genetics
MH  - Proto-Oncogene Proteins c-bcl-2/biosynthesis
MH  - RNA, Small Interfering/genetics
MH  - Stomach Neoplasms/*drug therapy/genetics/*metabolism/pathology
MH  - Transfection
MH  - Vincristine/*pharmacology
MH  - bcl-2-Associated X Protein/antagonists & inhibitors
EDAT- 2007/10/24 09:00
MHDA- 2008/02/19 09:00
CRDT- 2007/10/24 09:00
PHST- 2007/10/24 09:00 [pubmed]
PHST- 2008/02/19 09:00 [medline]
PHST- 2007/10/24 09:00 [entrez]
AID - CAS643 [pii]
AID - 10.1111/j.1349-7006.2007.00643.x [doi]
PST - ppublish
SO  - Cancer Sci. 2008 Jan;99(1):121-8. doi: 10.1111/j.1349-7006.2007.00643.x. Epub 
      2007 Oct 22.