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Treatment of eyelid epithelial neoplasm by targeting sonic hedgehog signaling: an experimental study.
- Source :
-
Japanese journal of ophthalmology [Jpn J Ophthalmol] 2006 Jul-Aug; Vol. 50 (4), pp. 305-311. - Publication Year :
- 2006
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Abstract
- Purpose: To evaluate the effect of cyclopamine, an inhibitor of the Sonic hedgehog (Shh) signal, on the growth of an epithelial neoplasm.<br />Methods: Chemically induced eyelid tumors in XPC-null mice (n=40) were treated daily with a subcutaneous injection of cyclopamine (1 mg/animal) for 7 days. The animals were killed after bromodeoxyuridine (BrdU) labeling, and the tumors were histologically examined. An in vitro study was conducted by using a squamous cell carcinoma (SCC) cell line. The SCC cells were treated with 0, 12.5, or 25.0 microg/ml recombinant Shh (rShh) and either 0 or 100 microM cyclopamine, and cell proliferation was evaluated by using an MTT assay. Cells from this cell line were also implanted subcutaneously in nude mice (n=8) to develop tumors, and the effect of cyclopamine administration was examined in the developed tumors.<br />Results: Histology showed that cyclopamine treatment suppressed BrdU incorporation and induced apoptosis in the majority of cells in tumors chemically induced in the eyelid of the XPC-null mice. Cell proliferation of the SCC cell line was enhanced by adding rShh, and this effect was abolished by adding cyclopamine. Proliferation of the SCC cell line was not affected by adding cyclopamine in the absence of rShh. On the other hand, the SCC cells expressed Shh in vivo in tumors developed in nude mice, but cyclopamine suppressed cell proliferation in the tumors, and the Shh-signaling pathway was inhibited by cyclopamine-induced apoptosis.<br />Conclusions: Cyclopamine inhibits proliferation and induces apoptosis in epithelial tumor cells in vivo. The Shh-signaling pathway may be a potential therapeutic target for patients with eyelid tumors.<br /> (Copyright (c) Japanese Ophthalmological Society 2006.)
- Subjects :
- Animals
Apoptosis drug effects
Carcinoma, Squamous Cell chemically induced
Carcinoma, Squamous Cell metabolism
Cell Line, Tumor
Cell Proliferation drug effects
Disease Models, Animal
Disease Progression
Eyelid Neoplasms chemically induced
Eyelid Neoplasms metabolism
Hedgehog Proteins
Humans
In Vitro Techniques
Male
Mice
Mice, Inbred C57BL
Trans-Activators metabolism
Treatment Outcome
Veratrum Alkaloids administration & dosage
Carcinoma, Squamous Cell drug therapy
Eyelid Neoplasms drug therapy
Eyelids pathology
Signal Transduction drug effects
Trans-Activators antagonists & inhibitors
Veratrum Alkaloids therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 0021-5155
- Volume :
- 50
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Japanese journal of ophthalmology
- Publication Type :
- Academic Journal
- Accession number :
- 16897213
- Full Text :
- https://doi.org/10.1007/s10384-006-0341-1