| Activation of Sonic hedgehog signaling pathway in S-type neuroblastoma cell lines. | |
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MedLine Citation:
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PMID: 20556567 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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The effects of Sonic hedgehog (Shh) signaling pathway activation on S-type neuroblastoma (NB) cell lines and its role in NB tumorigenesis were investigated. Immunohistochemistry was used to detect the expression of Shh pathway components-Patched1 (PTCH1) and Gli1 in 40 human primary NB samples. Western blotting and RT-PCR were used to examine the protein expression and mRNA levels of PTCH1 and Gli1 in three kinds of S-type NB cell lines (SK-N-AS, SK-N-SH and SHEP1), respectively. Exogenous Shh was administrated to activate Shh signaling pathway while cyclopamine was used as a selective antagonist of Shh pathway. S-type NB cell lines were treated with different concentrations of Shh or/and cyclopamine for different durations. Cell viability was measured by using MTT method. Apoptosis rate and cell cycle were assayed by flow cytometry. The xenograft experiments were used to evaluate the role of Shh pathway in tumor growth in immunodeficient mice. High-level expression of PTCH1 and Gli1 was detected in both NB samples and S-type NB cell lines. Cyclopamine decreased the survival rate of the three cell lines while Shh increased it, and the inhibition effects of cyclopamine could be partially reversed by shh pre-treatment. Cyclopamine induced the cell apoptosis and the cell cycle arrest in G0/G1 phase, while Shh induced the reverse effects and could partially prevent effects of cyclopamine. Cyclopamine could also inhibit the growth of NB in vivo. Our studies revealed that activation of the Shh pathway is important for survival and proliferation of S-type NB cells in vivo and in vitro through affecting cell apoptosis and cell cycle, suggesting a new therapeutic approach to NB. |
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Authors:
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Yunan Zhou; Ruolian Dai; Ling Mao; Yuanpeng Xia; Yufang Yao; Xue Yang; Bo Hu |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-17 |
Journal Detail:
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Title: Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban Volume: 30 ISSN: 1672-0733 ISO Abbreviation: J. Huazhong Univ. Sci. Technol. Med. Sci. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-06-17 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101169627 Medline TA: J Huazhong Univ Sci Technolog Med Sci Country: China |
Other Details:
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Languages: eng Pagination: 271-7 Citation Subset: IM |
Affiliation:
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Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, 430022. talent62@hotmail.com |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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