| Title |
Suppression of Cholangiocarcinoma Cell Growth by Human Umbilical Cord Mesenchymal Stem Cells: A Possible Role of Wnt and Akt Signaling
|
|---|---|
| Published in |
PLOS ONE, April 2013
|
| DOI | 10.1371/journal.pone.0062844 |
| Pubmed ID | |
| Authors |
Juan Liu, Guoqing Han, Hui Liu, Chengyong Qin |
| Abstract |
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 3β (phospho-GSK-3β(Ser9)), β-catenin, cyclin-D1, and c-myc were down-regulated. We further demonstrated that CHIR99021, a GSK-3β inhibitor reversed the suppressive effects of hUC-MSCs on HCCC-9810 cells and increased the expression of β-catenin. The GSK-3β activator, sodium nitroprusside dehydrate (SNP), augmented the anti-tumor effects of hUC-MSCs and decreased the expression of β-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/β-catenin and PI3K/Akt signaling pathway, with GSK-3β as the key enzyme bridging these pathways, may contribute to the inhibition of cholangiocarcinoma cells by hUC-MSCs. |
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 48 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 2% |
| Sri Lanka | 1 | 2% |
| Singapore | 1 | 2% |
| Unknown | 45 | 94% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 10 | 21% |
| Student > Ph. D. Student | 9 | 19% |
| Student > Master | 7 | 15% |
| Student > Bachelor | 4 | 8% |
| Student > Postgraduate | 3 | 6% |
| Other | 7 | 15% |
| Unknown | 8 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 11 | 23% |
| Agricultural and Biological Sciences | 11 | 23% |
| Biochemistry, Genetics and Molecular Biology | 9 | 19% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 2% |
| Chemical Engineering | 1 | 2% |
| Other | 3 | 6% |
| Unknown | 12 | 25% |