論文 - 詳細
RRC ID | 52248 |
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著者 | Fukushima S, Endo M, Matsumoto Y, Fukushi JI, Matsunobu T, Kawaguchi KI, Setsu N, IIda K, Yokoyama N, Nakagawa M, Yahiro K, Oda Y, Iwamoto Y, Nakashima Y. |
タイトル | Hypoxia-inducible factor 1 alpha is a poor prognostic factor and potential therapeutic target in malignant peripheral nerve sheath tumor. |
ジャーナル | PLoS One |
Abstract |
BACKGROUND:Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma with poor prognosis. Hypoxia-inducible factor 1 (HIF-1) plays a crucial role in the cellular response to hypoxia and regulates the expression of multiple genes involved in tumor progression in various cancers. However, the importance of the expression of HIF-1α in MPNSTs is unclear. METHODS:The expression of HIF-1α was examined immunohistochemically in 82 MPNST specimens. Cell culture assays of human MPNST cells under normoxic and hypoxic conditions were used to evaluate the impact of anti-HIF-1α-specific siRNA inhibition on cell survival. A screening kit was employed to identify small molecules that inhibited HIF-1α. RESULTS:The nuclear expression of HIF-1α was positive in 75.6% of MPNST samples (62/82 cases). Positivity for HIF-1α was a significant poor prognostic factor both in univariate (P = 0.048) and multivariate (P ≤ 0.0001) analyses. HIF-1α knockdown abrogated MPNST cell growth, inducing apoptosis. Finally, chetomin, an inhibitor of HIF-1α, effectively inhibited the growth of MPNST cells and induced their apoptosis. CONCLUSION:Inhibition of HIF-1α signaling is a potential treatment option for MPNSTs. |
巻・号 | 12(5) |
ページ | e0178064 |
公開日 | 2017-5-30 |
DOI | 10.1371/journal.pone.0178064 |
PII | PONE-D-17-00673 |
PMID | 28558056 |
PMC | PMC5448771 |
MeSH | Cell Line, Tumor Cell Proliferation Female Humans Hypoxia-Inducible Factor 1, alpha Subunit / genetics Hypoxia-Inducible Factor 1, alpha Subunit / metabolism* Male Middle Aged Neurilemmoma / metabolism* Neurilemmoma / pathology Neurilemmoma / therapy Oxygen / metabolism Polymerase Chain Reaction Prognosis RNA, Small Interfering / genetics |
IF | 2.74 |
引用数 | 7 |
リソース情報 | |
ヒト・動物細胞 | HS-Sch-2(RCB2230) |