Identification of drug candidate against prostate cancer from the aspect of somatic cell reprogramming
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- Takeo Kosaka
- Department of Urology The Sakaguchi Laboratory School of Medicine Keio University Tokyo Japan
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- Go Nagamatsu
- Department of Cell Differentiation The Sakaguchi Laboratory School of Medicine Keio University Tokyo Japan
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- Shigeru Saito
- Molecular Profiling Research Center for Drug Discovery (molprof) National Institute of Advanced Industrial Science and Technology (AIST) Tokyo Japan
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- Mototsugu Oya
- Department of Urology The Sakaguchi Laboratory School of Medicine Keio University Tokyo Japan
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- Toshio Suda
- Department of Cell Differentiation The Sakaguchi Laboratory School of Medicine Keio University Tokyo Japan
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- Katsuhisa Horimoto
- Molecular Profiling Research Center for Drug Discovery (molprof) National Institute of Advanced Industrial Science and Technology (AIST) Tokyo Japan
この論文をさがす
説明
<jats:p>Considering the similarities between the transcriptional programming involved in cancer progression and somatic cell reprogramming, we tried to identify drugs that would be effective against malignant cancers. We used the early transposon Oct4 and Sox2 enhancer (<jats:styled-content style="fixed-case">EOS</jats:styled-content>) system to select human prostate cancer (<jats:styled-content style="fixed-case">PCA</jats:styled-content>) cells expressing high levels of <jats:styled-content style="fixed-case">OCT</jats:styled-content>4. Patients with metastatic castration‐resistant <jats:styled-content style="fixed-case">PCA</jats:styled-content> that does not respond to treatment with docetaxel have few therapeutic options. The <jats:styled-content style="fixed-case">OCT</jats:styled-content>4‐expressing <jats:styled-content style="fixed-case">PCA</jats:styled-content> cells selected using the <jats:styled-content style="fixed-case">EOS</jats:styled-content> system showed increased tumorigenicity and high resistance to docetaxel, both <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic>. By using their gene expression data, expression signature‐based prediction for compound candidates identified an antiviral drug, ribavirin, as a conversion modulator from drug resistance to sensitivity. Treatment of <jats:styled-content style="fixed-case">PCA</jats:styled-content> cells with ribavirin decreased their resistance against treatment with docetaxel. This indicated that ribavirin reversed the gene expression, including that of humoral factors, in the <jats:styled-content style="fixed-case">OCT</jats:styled-content>4‐expressing <jats:styled-content style="fixed-case">PCA</jats:styled-content> cells selected using the <jats:styled-content style="fixed-case">EOS</jats:styled-content> system. Thereby, ribavirin increased the efficacy of docetaxel for cancer cells. We propose a novel cell reprogramming approach, named drug efficacy reprogramming, as a new model for identifying candidate antitumor drugs.</jats:p>
収録刊行物
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- Cancer Science
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Cancer Science 104 (8), 1017-1026, 2013-05-26
Wiley
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キーワード
- Male
- SOXB1 Transcription Factors
- Mice, Nude
- Antineoplastic Agents
- Docetaxel
- Cellular Reprogramming
- Xenograft Model Antitumor Assays
- Mice
- Prostatic Neoplasms, Castration-Resistant
- Drug Resistance, Neoplasm
- Cell Line, Tumor
- Ribavirin
- Animals
- Humans
- Taxoids
- Drug Screening Assays, Antitumor
- Octamer Transcription Factor-3
詳細情報 詳細情報について
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- CRID
- 1360002218145925248
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- ISSN
- 13497006
- 13479032
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- PubMed
- 23600803
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
- OpenAIRE
