PMID- 23646150
OWN - NLM
STAT- MEDLINE
DCOM- 20131126
LR  - 20240319
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 4
DP  - 2013
TI  - Suppression of cholangiocarcinoma cell growth by human umbilical cord mesenchymal 
      stem cells: a possible role of Wnt and Akt signaling.
PG  - e62844
LID - 10.1371/journal.pone.0062844 [doi]
LID - e62844
AB  - Emerging evidence indicates that human mesenchymal stem cells (hMSCs) can be 
      recruited to tumor sites, and affect the growth of human malignancies. However, 
      little is known about the underlying molecular mechanisms. Here, we observed the 
      effects of hMSCs on the human cholangiocarcinoma cell line, HCCC-9810, using an 
      animal transplantation model, and conditioned media from human umbilical 
      cord-derived mesenchymal stem cells (hUC-MSCs). Animal studies showed that 
      hUC-MSCs can inhibit the growth of cholangiocarcinoma xenograft tumors. In cell 
      culture, conditioned media from hUC-MSCs inhibited proliferation and induced 
      apoptosis of tumor cells in a dose- and time-dependent manner. The proliferation 
      inhibition rate increased from 6.21% to 49.86%, whereas the apoptosis rate 
      increased from 9.3% to 48.1% when HCCC-9810 cells were cultured with 50% hUC-MSC 
      conditioned media for 24 h. Immunoblot analysis showed that the expression of 
      phosphor-PDK1 (Ser241), phosphor-Akt (Ser 437 and Thr308), phosphorylated 
      glycogen synthase kinase 3beta (phospho-GSK-3beta(Ser9)), beta-catenin, cyclin-D1, and 
      c-myc were down-regulated. We further demonstrated that CHIR99021, a GSK-3beta 
      inhibitor reversed the suppressive effects of hUC-MSCs on HCCC-9810 cells and 
      increased the expression of beta-catenin. The GSK-3beta activator, sodium nitroprusside 
      dehydrate (SNP), augmented the anti-tumor effects of hUC-MSCs and decreased the 
      expression of beta-catenin. IGF-1 acted as an Akt activator, and also reversed the 
      suppressive effects of hUC-MSCs on HCCC-9810 cells. All these results suggest 
      that hUC-MSCs could inhibit the malignant phenotype of HCCC-9810 human 
      cholangiocarcinoma cell line. The cross-talk role of Wnt/beta-catenin and PI3K/Akt 
      signaling pathway, with GSK-3beta as the key enzyme bridging these pathways, may 
      contribute to the inhibition of cholangiocarcinoma cells by hUC-MSCs.
FAU - Liu, Juan
AU  - Liu J
AD  - Department of Gastroenterology, Provincial Hospital Affiliated to Shandong 
      University, Jinan, China.
FAU - Han, Guoqing
AU  - Han G
FAU - Liu, Hui
AU  - Liu H
FAU - Qin, Chengyong
AU  - Qin C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130430
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Wnt Proteins)
RN  - 0 (beta Catenin)
RN  - EC 2.7.11.1 (GSK3B protein, human)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
EIN - PLoS One. 2013;8(7). doi:10.1371/annotation/7fff93fa-8e80-41f3-b35a-e658cb7256a9
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Bile Duct Neoplasms/*metabolism
MH  - Bile Ducts, Intrahepatic
MH  - Cell Differentiation
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cholangiocarcinoma/*metabolism
MH  - Culture Media, Conditioned/pharmacology/toxicity
MH  - Disease Models, Animal
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Humans
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/cytology/*metabolism
MH  - Mice
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - *Signal Transduction/drug effects
MH  - Umbilical Cord/cytology
MH  - Wnt Proteins/*metabolism
MH  - Xenograft Model Antitumor Assays
MH  - beta Catenin/metabolism
PMC - PMC3639969
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/05/07 06:00
MHDA- 2013/12/16 06:00
PMCR- 2013/04/30
CRDT- 2013/05/07 06:00
PHST- 2012/09/06 00:00 [received]
PHST- 2013/03/27 00:00 [accepted]
PHST- 2013/05/07 06:00 [entrez]
PHST- 2013/05/07 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
PHST- 2013/04/30 00:00 [pmc-release]
AID - PONE-D-12-27292 [pii]
AID - 10.1371/journal.pone.0062844 [doi]
PST - epublish
SO  - PLoS One. 2013 Apr 30;8(4):e62844. doi: 10.1371/journal.pone.0062844. Print 2013.