PMID- 24757411
OWN - NLM
STAT- MEDLINE
DCOM- 20150126
LR  - 20211021
IS  - 1537-744X (Electronic)
IS  - 2356-6140 (Print)
IS  - 1537-744X (Linking)
VI  - 2014
DP  - 2014
TI  - Fragile histidine triad (FHIT) suppresses proliferation and promotes apoptosis in 
      cholangiocarcinoma cells by blocking PI3K-Akt pathway.
PG  - 179698
LID - 10.1155/2014/179698 [doi]
LID - 179698
AB  - Fragile histidine triad (FHIT) is a tumor suppressor protein that regulates 
      cancer cell proliferation and apoptosis. However, its exact mechanism of action 
      is poorly understood. Phosphatidylinositol 3-OH kinase (PI3K)-Akt-survivin is an 
      important signaling pathway that was regulated by FHIT in lung cancer cells. To 
      determine whether FHIT can regulate this pathway in cholangiocarcinoma QBC939 
      cells, we constructed an FHIT expression plasmid and used it to transfect QBC939 
      cells. Protein and mRNA expression were measured by western blotting and qRT-PCR, 
      respectively. The viability and apoptosis of QBC939 cells were then assessed 
      using MTT assays and flow cytometry. Our results revealed that the expression of 
      survivin and Bcl-2 was downregulated, and caspase 3 was upregulated, in cells 
      overexpressing FHIT. In addition, FHIT suppressed the phosphorylation of Akt. The 
      changes in cell proliferation and apoptosis were obvious in cells overexpressing 
      FHIT which parallels that of treatment with LY294002, a potent inhibitor of 
      phosphoinositide 3-kinases. Treatment with LY294002 further decreased the 
      expression of survivin and Bcl-2 and increased caspase-3 levels. These results 
      suggest that FHIT can block the PI3K-Akt-survivin pathway by suppressing the 
      phosphorylation of Akt and the expression of survivin and Bcl-2 and upregulating 
      caspase 3.
FAU - Huang, Qiang
AU  - Huang Q
AD  - Department of General Surgery, Qilu Hospital of Shandong University, No. 107 
      Wenhuaxi Road, Jinan 250012, China.
FAU - Liu, Zhen
AU  - Liu Z
AD  - Department of General Surgery, Anhui Provincial Hospital Affiliated with Anhui 
      Medical University, Hefei, Anhui 230001, China ; Hepatic-Biliary-Pancreatic Key 
      Laboratory of Anhui Province, Hefei, Anhui 230001, China.
FAU - Xie, Fang
AU  - Xie F
AD  - Department of General Surgery, Anhui Provincial Hospital Affiliated with Anhui 
      Medical University, Hefei, Anhui 230001, China ; Hepatic-Biliary-Pancreatic Key 
      Laboratory of Anhui Province, Hefei, Anhui 230001, China.
FAU - Liu, Chenhai
AU  - Liu C
AD  - Department of General Surgery, Anhui Provincial Hospital Affiliated with Anhui 
      Medical University, Hefei, Anhui 230001, China ; Hepatic-Biliary-Pancreatic Key 
      Laboratory of Anhui Province, Hefei, Anhui 230001, China.
FAU - Shao, Feng
AU  - Shao F
AD  - Department of General Surgery, Anhui Provincial Hospital Affiliated with Anhui 
      Medical University, Hefei, Anhui 230001, China ; Hepatic-Biliary-Pancreatic Key 
      Laboratory of Anhui Province, Hefei, Anhui 230001, China.
FAU - Zhu, Cheng-lin
AU  - Zhu CL
AD  - Department of General Surgery, Anhui Provincial Hospital Affiliated with Anhui 
      Medical University, Hefei, Anhui 230001, China ; Hepatic-Biliary-Pancreatic Key 
      Laboratory of Anhui Province, Hefei, Anhui 230001, China.
FAU - Hu, Sanyuan
AU  - Hu S
AD  - Department of General Surgery, Qilu Hospital of Shandong University, No. 107 
      Wenhuaxi Road, Jinan 250012, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140316
PL  - United States
TA  - ScientificWorldJournal
JT  - TheScientificWorldJournal
JID - 101131163
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (fragile histidine triad protein)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.6.- (Acid Anhydride Hydrolases)
SB  - IM
MH  - Acid Anhydride Hydrolases/*biosynthesis
MH  - Apoptosis/*physiology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/*physiology
MH  - Cholangiocarcinoma/*metabolism/prevention & control
MH  - Humans
MH  - Neoplasm Proteins/*biosynthesis
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Proto-Oncogene Proteins c-akt/*antagonists & inhibitors/metabolism
MH  - Signal Transduction/physiology
PMC - PMC3976809
EDAT- 2014/04/24 06:00
MHDA- 2015/01/27 06:00
PMCR- 2014/03/16
CRDT- 2014/04/24 06:00
PHST- 2014/01/02 00:00 [received]
PHST- 2014/02/17 00:00 [accepted]
PHST- 2014/04/24 06:00 [entrez]
PHST- 2014/04/24 06:00 [pubmed]
PHST- 2015/01/27 06:00 [medline]
PHST- 2014/03/16 00:00 [pmc-release]
AID - 10.1155/2014/179698 [doi]
PST - epublish
SO  - ScientificWorldJournal. 2014 Mar 16;2014:179698. doi: 10.1155/2014/179698. 
      eCollection 2014.