{"created":"2025-01-27T04:55:54.807039+00:00","id":2001707,"links":{},"metadata":{"_buckets":{"deposit":"589fc824-940f-46d5-9e3f-e454eb3433b9"},"_deposit":{"created_by":10,"id":"2001707","owners":[10],"pid":{"revision_id":0,"type":"depid","value":"2001707"},"status":"published"},"_oai":{"id":"oai:repository.lib.tottori-u.ac.jp:02001707","sets":["1:7","2:12"]},"author_link":["4668"],"item_30002_access_rights4":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_30002_bibliographic_information29":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2023-08-23","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"3","bibliographicNumberOfPages":"9","bibliographicPageEnd":"112","bibliographicPageStart":"104","bibliographicVolumeNumber":"153","bibliographic_titles":[{"bibliographic_title":"Journal of pharmacological sciences","bibliographic_titleLang":"en"}]}]},"item_30002_creator2":{"attribute_name":"作成者","attribute_type":"creator","attribute_value_mlt":[{"creatorAffiliations":[{"affiliationNameIdentifiers":[{"affiliationNameIdentifier":"15101","affiliationNameIdentifierScheme":"kakenhi"}],"affiliationNames":[{"affiliationName":"鳥取大学","affiliationNameLang":"ja"},{"affiliationName":"Tottori University","affiliationNameLang":"en"}]}],"creatorNames":[{"creatorName":"Tashiro,Jiro","creatorNameLang":"en","creatorNameType":"Personal"}],"familyNames":[{"familyName":"Tashiro","familyNameLang":"en"}],"givenNames":[{"givenName":"Jiro","givenNameLang":"en"}]},{"creatorAffiliations":[{"affiliationNameIdentifiers":[{"affiliationNameIdentifier":"15101","affiliationNameIdentifierScheme":"kakenhi"}],"affiliationNames":[{"affiliationName":"鳥取大学","affiliationNameLang":"ja"},{"affiliationName":"Tottori University","affiliationNameLang":"en"}]}],"creatorNames":[{"creatorName":"Sugiura,Akihiro","creatorNameLang":"en","creatorNameType":"Personal"}],"familyNames":[{"familyName":"Sugiura","familyNameLang":"en"}],"givenNames":[{"givenName":"Akihiro","givenNameLang":"en"}]},{"creatorNames":[{"creatorName":"Warita,Tomoko","creatorNameLang":"en","creatorNameType":"Personal"}],"familyNames":[{"familyName":"Warita","familyNameLang":"en"}],"givenNames":[{"givenName":"Tomoko","givenNameLang":"en"}]},{"creatorNames":[{"creatorName":"Irie,Nanami","creatorNameLang":"en","creatorNameType":"Personal"}],"familyNames":[{"familyName":"Irie","familyNameLang":"en"}],"givenNames":[{"givenName":"Nanami","givenNameLang":"en"}]},{"creatorAffiliations":[{"affiliationNameIdentifiers":[{"affiliationNameIdentifier":"15101","affiliationNameIdentifierScheme":"kakenhi"}],"affiliationNames":[{"affiliationName":"鳥取大学","affiliationNameLang":"ja"},{"affiliationName":"Tottori University","affiliationNameLang":"en"}]}],"creatorNames":[{"creatorName":"Dwi Cahyadi,Danang","creatorNameLang":"en","creatorNameType":"Personal"}],"familyNames":[{"familyName":"Dwi Cahyadi","familyNameLang":"en"}],"givenNames":[{"givenName":"Danang","givenNameLang":"en"}]},{"creatorNames":[{"creatorName":"Ishikawa,Takuro","creatorNameLang":"en","creatorNameType":"Personal"}],"familyNames":[{"familyName":"Ishikawa","familyNameLang":"en"}],"givenNames":[{"givenName":"Takuro","givenNameLang":"en"}]},{"creatorAffiliations":[{"affiliationNameIdentifiers":[{"affiliationNameIdentifier":"15101","affiliationNameIdentifierScheme":"kakenhi"}],"affiliationNames":[{"affiliationName":"鳥取大学","affiliationNameLang":"ja"},{"affiliationName":"Tottori University","affiliationNameLang":"en"}]}],"creatorNames":[{"creatorName":"割田,克彦","creatorNameLang":"ja","creatorNameType":"Personal"},{"creatorName":"Warita,Katsuhiko","creatorNameLang":"en","creatorNameType":"Personal"},{"creatorName":"ワリタ,カツヒコ","creatorNameLang":"ja-Kana","creatorNameType":"Personal"}],"familyNames":[{"familyName":"割田","familyNameLang":"ja"},{"familyName":"Warita","familyNameLang":"en"},{"familyName":"ワリタ","familyNameLang":"ja-Kana"}],"givenNames":[{"givenName":"克彦","givenNameLang":"ja"},{"givenName":"Katsuhiko","givenNameLang":"en"},{"givenName":"カツヒコ","givenNameLang":"ja-Kana"}],"nameIdentifiers":[{"nameIdentifier":"4668","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"100001516","nameIdentifierScheme":"研究者総覧鳥取大学","nameIdentifierURI":"http://researchers.adm.tottori-u.ac.jp/html/100001516_ja.html"},{"nameIdentifier":"40452669","nameIdentifierScheme":"e-Rad_Researcher","nameIdentifierURI":"https://kaken.nii.ac.jp/ja/search/?qm=40452669"}]}]},"item_30002_date11":{"attribute_name":"日付","attribute_value_mlt":[{"subitem_date_issued_datetime":"2023-08-23","subitem_date_issued_type":"Issued"}]},"item_30002_description9":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"Statins, which are cholesterol synthesis inhibitors, are well-known therapeutics for dyslipidemia; however, some studies have anticipated their use as anticancer agents. However, epithelial cancer cells show strong resistance to statins through an increased expression of HMG-CoA reductase (HMGCR), an inhibitory target of statins. Castration-resistant prostate cancer (CRPC) cells synthesize androgens from cholesterol on their own. We performed suppression of CYP11A1, a rate-limiting enzyme in androgen synthesis from cholesterol, using siRNA or inhibitors, to examine the effect of steroidogenesis inhibition on statin sensitivity in CRPC cells. Here, we suggested that CYP11A1 silencing sensitized the statin-resistant CRPC cell line DU-145 to atorvastatin via HMGCR downregulation by an increase in intracellular free cholesterol. We further demonstrated that CYP11A1 silencing induced epithelial-mesenchymal transition, which converted DU-145 cells into a statin-sensitive phenotype. This suggests that concomitant use of CYP11A1 inhibitors could be an effective approach for overcoming statin resistance in CRPC. Moreover, we showed that ketoconazole, a CYP11A1 inhibitor, sensitized DU-145 cells to atorvastatin, although not all the molecular events observed in CYP11A1 silencing were reproducible. Although further studies are necessary to clarify the detailed mechanisms, ketoconazole may be effective as a concomitant drug that potentiates the anticancer effect of atorvastatin.","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_30002_file35":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2023-08-23"}],"displaytype":"detail","fileDate":[{"fileDateType":"Issued","fileDateValue":"2023-08-23"}],"filename":"jps153(3)_104.pdf","filesize":[{"value":"1.8 MB"}],"format":"application/pdf","licensefree":"(C) 2023 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).","licensetype":"license_0","mimetype":"application/pdf","url":{"objectType":"fulltext","url":"https://repository.lib.tottori-u.ac.jp/record/2001707/files/jps153(3)_104.pdf"},"version_id":"088590a5-9dfc-4a16-bec3-3653afce8090"}]},"item_30002_issue_number25":{"attribute_name":"号","attribute_value_mlt":[{"subitem_issue":"3"}]},"item_30002_language12":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_30002_number_of_pages26":{"attribute_name":"ページ数","attribute_value_mlt":[{"subitem_number_of_pages":"9"}]},"item_30002_page_end28":{"attribute_name":"終了ページ","attribute_value_mlt":[{"subitem_end_page":"112"}]},"item_30002_page_start27":{"attribute_name":"開始ページ","attribute_value_mlt":[{"subitem_start_page":"104"}]},"item_30002_publisher10":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Elsevier BV","subitem_publisher_language":"en"}]},"item_30002_relation18":{"attribute_name":"関連情報","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1016/j.jphs.2023.08.002","subitem_relation_type_select":"DOI"}}]},"item_30002_resource_type13":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_30002_rights6":{"attribute_name":"権利情報","attribute_value_mlt":[{"subitem_rights":"(C) 2023 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).","subitem_rights_language":"en"}]},"item_30002_source_identifier22":{"attribute_name":"収録物識別子","attribute_value_mlt":[{"subitem_source_identifier":"13478648","subitem_source_identifier_type":"EISSN"},{"subitem_source_identifier":"13478613","subitem_source_identifier_type":"PISSN"}]},"item_30002_source_title23":{"attribute_name":"収録物名","attribute_value_mlt":[{"subitem_source_title":"Journal of pharmacological sciences","subitem_source_title_language":"en"}]},"item_30002_subject8":{"attribute_name":"主題","attribute_value_mlt":[{"subitem_subject":"Statin","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"CRPC","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"HMGCR","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Cholesterol","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"EMT","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_30002_title0":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"CYP11A1 silencing suppresses HMGCR expression via cholesterol accumulation and sensitizes CRPC cell line DU-145 to atorvastatin","subitem_title_language":"en"}]},"item_30002_version_type15":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_30002_volume_number24":{"attribute_name":"巻","attribute_value_mlt":[{"subitem_volume":"153"}]},"item_title":"CYP11A1 silencing suppresses HMGCR expression via cholesterol accumulation and sensitizes CRPC cell line DU-145 to atorvastatin","item_type_id":"30002","owner":"10","path":["12","7"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2025-02-12"},"publish_date":"2025-02-12","publish_status":"0","recid":"2001707","relation_version_is_last":true,"title":["CYP11A1 silencing suppresses HMGCR expression via cholesterol accumulation and sensitizes CRPC cell line DU-145 to atorvastatin"],"weko_creator_id":"10","weko_shared_id":-1},"updated":"2025-02-13T08:19:31.563681+00:00"}