PMID- 22471589
OWN - NLM
STAT- MEDLINE
DCOM- 20120904
LR  - 20211021
IS  - 1423-0127 (Electronic)
IS  - 1021-7770 (Print)
IS  - 1021-7770 (Linking)
VI  - 19
IP  - 1
DP  - 2012 Apr 3
TI  - Depletion of OLFM4 gene inhibits cell growth and increases sensitization to 
      hydrogen peroxide and tumor necrosis factor-alpha induced-apoptosis in gastric 
      cancer cells.
PG  - 38
LID - 10.1186/1423-0127-19-38 [doi]
AB  - BACKGROUND: Human olfactomedin 4 (OLFM4) gene is a secreted glycoprotein more 
      commonly known as the anti-apoptotic molecule GW112. OLFM4 is found to be 
      frequently up-regulated in many types of human tumors including gastric cancer 
      and it was believed to play significant role in the progression of gastric 
      cancer. Although the function of OLFM4 has been indicated in many studies, recent 
      evidence strongly suggests a cell or tissue type-dependent role of OLFM4 in cell 
      growth and apoptosis. The aim of this study is to examine the role of gastric 
      cancer-specific expression of OLFM4 in cell growth and apoptosis resistance. 
      METHODS: OLFM4 expression was eliminated by RNA interference in SGC-7901 and 
      MKN45 cells. Cell proliferation, anchorage-independent growth, cell cycle and 
      apoptosis were characterized in vitro. Tumorigenicity was analyzed in vivo. The 
      apoptosis and caspase-3 activation in response to hydrogen peroxide (H2O2) or 
      tumor necrosis factor-alpha (TNF alpha) were assessed in the presence or absence of 
      caspase inhibitor Z-VAD-fmk. RESULTS: The elimination of OLFM4 protein by RNA 
      interference in SGC-7901 and MKN45 cells significantly inhibits tumorigenicity 
      both in vitro and in vivo by induction of cell G1 arrest (all P < 0.01). OLFM4 
      knockdown did not trigger obvious cell apoptosis but increased H2O2 or TNF 
      alpha-induced apoptosis and caspase-3 activity (all P < 0.01). Treatment of Z-VAD-fmk 
      attenuated caspase-3 activity and significantly reversed the H(2)O(2) or TNF 
      alpha-induced apoptosis in OLFM4 knockdown cells (all P < 0.01). CONCLUSION: Our 
      study suggests that depletion of OLFM4 significantly inhibits tumorigenicity of 
      the gastric cancer SGC-7901 and MKN45 cells. Blocking OLFM4 expression can 
      sensitize gastric cancer cells to H2O2 or TNF alpha treatment by increasing caspase-3 
      dependent apoptosis. A combination strategy based on OLFM4 inhibition and 
      anticancer drugs treatment may provide therapeutic potential in gastric cancer 
      intervention.
FAU - Liu, Rui-hua
AU  - Liu RH
AD  - Center for Clinical Molecular Medicine, Ministry of Education Key Laboratory of 
      Child Development and Disorders, Chongqing International Science and Technology 
      Cooperation Center for Child Development and Disorders, Children's Hospital, 
      Chongqing Medical University, Chongqing 400014, China.
FAU - Yang, Mei-hua
AU  - Yang MH
FAU - Xiang, Hua
AU  - Xiang H
FAU - Bao, Li-ming
AU  - Bao LM
FAU - Yang, Hua-an
AU  - Yang HA
FAU - Yue, Li-wen
AU  - Yue LW
FAU - Jiang, Xue
AU  - Jiang X
FAU - Ang, Na
AU  - Ang N
FAU - Wu, Li-ya
AU  - Wu LY
FAU - Huang, Yi
AU  - Huang Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120403
PL  - England
TA  - J Biomed Sci
JT  - Journal of biomedical science
JID - 9421567
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (OLFM4 protein, human)
RN  - 0 (Oxidants)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone)
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Amino Acid Chloromethyl Ketones/pharmacology
MH  - Apoptosis/*drug effects/genetics
MH  - Caspase Inhibitors
MH  - Caspases/metabolism
MH  - Cell Cycle Checkpoints/drug effects/genetics
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - G1 Phase/drug effects/genetics
MH  - Gene Deletion
MH  - Granulocyte Colony-Stimulating Factor/genetics/*metabolism
MH  - Humans
MH  - Hydrogen Peroxide/*pharmacology
MH  - Oxidants/*pharmacology
MH  - RNA Interference
MH  - Stomach Neoplasms/genetics/*metabolism/pathology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
PMC - PMC3359197
EDAT- 2012/04/05 06:00
MHDA- 2012/09/05 06:00
PMCR- 2012/04/03
CRDT- 2012/04/05 06:00
PHST- 2011/12/03 00:00 [received]
PHST- 2012/04/03 00:00 [accepted]
PHST- 2012/04/05 06:00 [entrez]
PHST- 2012/04/05 06:00 [pubmed]
PHST- 2012/09/05 06:00 [medline]
PHST- 2012/04/03 00:00 [pmc-release]
AID - 1423-0127-19-38 [pii]
AID - 10.1186/1423-0127-19-38 [doi]
PST - epublish
SO  - J Biomed Sci. 2012 Apr 3;19(1):38. doi: 10.1186/1423-0127-19-38.