Abstract | PURPOSE: METHODS: Human hilar cholangiocarcinoma cells KKU-100 were treated with PI3K inhibitors, and cell viability and apoptosis assays were performed. The expression of a MAPK phosphatase (MKP-1) that contributes to cancer cell survival in response to multiple stress stimuli was assayed by quantitative real-time RT-PCR and western blotting. In addition, the effects of the MKP-1 inhibitor were studied in KKU-100 cells treated with PI3K inhibitors. RESULTS: Incubation of KKU-100 cells with PI3K inhibitors resulted in increased expression of MKP-1. Furthermore, we found that inhibition of MKP-1 using siRNA silencing sensitized KKU-100 cells to PI3K inhibitor-induced apoptosis via increased phosphorylation of p38 MAPK. CONCLUSIONS: These results indicate that concurrent inhibition of PI3K and MKP-1 induces apoptosis in KKU-100 cells. Simultaneous targeting of the PI3K pathway and MKP-1 may be a useful approach to improve therapies directed against hilar cholangiocarcinoma.
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Authors | Kawin Leelawat, Wandee Udomchaiprasertkul, Siriluck Narong, Surang Leelawat |
Journal | Journal of cancer research and clinical oncology
(J Cancer Res Clin Oncol)
Vol. 136
Issue 10
Pg. 1537-44
(Oct 2010)
ISSN: 1432-1335 [Electronic] Germany |
PMID | 20145951
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Chromones
- Morpholines
- Phosphoinositide-3 Kinase Inhibitors
- 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
- Cycloheximide
- p38 Mitogen-Activated Protein Kinases
- DUSP1 protein, human
- Dual Specificity Phosphatase 1
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Topics |
- Bile Duct Neoplasms
(drug therapy, pathology)
- Bile Ducts, Intrahepatic
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Cholangiocarcinoma
(drug therapy, pathology)
- Chromones
(pharmacology)
- Cycloheximide
(pharmacology)
- Dual Specificity Phosphatase 1
(genetics, physiology)
- Humans
- Morpholines
(pharmacology)
- Phosphatidylinositol 3-Kinases
(physiology)
- Phosphoinositide-3 Kinase Inhibitors
- Phosphorylation
- p38 Mitogen-Activated Protein Kinases
(metabolism)
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