{"paper_id":"4dc748ff-6759-443a-9b72-3df29a2f00fc","body_text":"Cordycepin Enhances Paclitaxel Sensitivity in TNBC by Targeting the HIF-1α/RAD51 DNA Repair Feedback Loop | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Cordycepin Enhances Paclitaxel Sensitivity in TNBC by Targeting the HIF-1α/RAD51 DNA Repair Feedback Loop Yue Li, Yannan Fu, Jiyu Yang, Xianchun Zhou, Lin Chen, Zhenhua Lin, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9355031/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Triple-negative breast cancer (TNBC) remains a serious global health burden for women, with an increasing incidence and a longstanding lack of effective therapeutic strategies. These unmet clinical needs highlight the urgent need to develop novel chemosensitizers and elucidate their underlying molecular mechanisms. Cordycepin(a natural bioactive compound) has been previously reported to exert synergistic anti-tumor effects in various malignant tumors. The present study aims to clarify the chemosensitizing mechanism of cordycepin in TNBC, which is characterized by high invasiveness and strong adaptability to hypoxia. Our results demonstrated that cordycepin significantly enhanced the cytotoxicity of paclitaxel in TNBC cells by inhibiting the HIF-1α/RAD51 positive feedback loop, a key driver of TNBC progression, thereby blocking DNA repair. These findings uncover a novel mechanistic role of cordycepin in enhancing chemosensitivity, providing a promising therapeutic strategy for improving clinical outcomes in patients with TNBC. Biological sciences/Cancer Biological sciences/Drug discovery Health sciences/Oncology Cordycepin paclitaxel triple-negative breast cancer HIF-1α/RAD51 DNA repair Chemotherapy sensitivity Full Text Additional Declarations No competing interests reported. Supplementary Files SFigure1.png SFigure201.png SFigure301.png Wb.pdf Figurelegends.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 21 Apr, 2026 Editor assigned by journal 19 Apr, 2026 Submission checks completed at journal 13 Apr, 2026 First submitted to journal 08 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-9355031\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Article\",\"associatedPublications\":[],\"authors\":[{\"id\":626865429,\"identity\":\"92c4e096-c8c8-4a12-8a3d-d602b19138c6\",\"order_by\":0,\"name\":\"Yue Li\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Yanbian university\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yue\",\"middleName\":\"\",\"lastName\":\"Li\",\"suffix\":\"\"},{\"id\":626865430,\"identity\":\"f4fe2c09-a5da-4c17-9c30-d2e50ee5edc5\",\"order_by\":1,\"name\":\"Yannan Fu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Yanbian university\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yannan\",\"middleName\":\"\",\"lastName\":\"Fu\",\"suffix\":\"\"},{\"id\":626865432,\"identity\":\"eb88cbc2-a258-48b9-b68e-9019468683a6\",\"order_by\":2,\"name\":\"Jiyu Yang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Yanbian university\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Jiyu\",\"middleName\":\"\",\"lastName\":\"Yang\",\"suffix\":\"\"},{\"id\":626865434,\"identity\":\"3e4bb36d-b588-4ee2-ae43-80640db78718\",\"order_by\":3,\"name\":\"Xianchun Zhou\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Yanbian university\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Xianchun\",\"middleName\":\"\",\"lastName\":\"Zhou\",\"suffix\":\"\"},{\"id\":626865435,\"identity\":\"2d1c74d3-7159-432c-b0a5-3dc7a28ab099\",\"order_by\":4,\"name\":\"Lin Chen\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Yanbian university\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Lin\",\"middleName\":\"\",\"lastName\":\"Chen\",\"suffix\":\"\"},{\"id\":626865436,\"identity\":\"0db7699f-fd71-481f-bbbc-31bf9c7357d9\",\"order_by\":5,\"name\":\"Zhenhua Lin\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Yanbian university\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Zhenhua\",\"middleName\":\"\",\"lastName\":\"Lin\",\"suffix\":\"\"},{\"id\":626865437,\"identity\":\"5938e787-a59c-4a03-884f-7dc4d424245c\",\"order_by\":6,\"name\":\"Yang Yang\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5ElEQVRIiWNgGAWjYDADfgYeEMVMghbJBpK1GBwgVovB8bOHX/PU3LHbfCP3mARDhXViA/vZA/i1nMlLs+Y59ix52428NAmGM+mJDTx5CQTck2NmzMN2ONnsRo6ZBGPb4cQGCR4D/FrOvwFq+Xc42XgGSMs/YrTcyDF+zNt22M5AAqSlgQgtkjfemDHO7TucIHHmXbJFwrF04zaeHPxa+M7nGH948+2wPX977sEbH2qsZfvZz+DXonCAgU0KGCOJDQIJDAxAxMCGVz0QyDcwMH/8wcBgz8B/gJDaUTAKRsEoGKkAAApwSZ4rQEAXAAAAAElFTkSuQmCC\",\"orcid\":\"\",\"institution\":\"Yanbian university\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Yang\",\"middleName\":\"\",\"lastName\":\"Yang\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2026-04-08 09:53:00\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-9355031/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-9355031/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":108184936,\"identity\":\"2ef7ed9f-64ce-4aa3-8bf0-8225df291408\",\"added_by\":\"auto\",\"created_at\":\"2026-04-30 09:05:05\",\"extension\":\"pdf\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":1016152,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"TNBC.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-9355031/v1_covered_db746e33-8e91-44f3-87bd-de78910d6b72.pdf\"},{\"id\":108183411,\"identity\":\"497405b3-5a48-41e3-afb4-d80723175a03\",\"added_by\":\"auto\",\"created_at\":\"2026-04-30 09:00:54\",\"extension\":\"png\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":29391848,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"SFigure1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-9355031/v1/6e8e89ea790b365948925f9d.png\"},{\"id\":108183538,\"identity\":\"da4b2ce3-dfbd-476a-8267-4f670feb614b\",\"added_by\":\"auto\",\"created_at\":\"2026-04-30 09:01:58\",\"extension\":\"png\",\"order_by\":2,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":7070726,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"SFigure201.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-9355031/v1/f9eec87b682fe7cdd8b7bb0b.png\"},{\"id\":108184308,\"identity\":\"dc05c6d3-e0b4-46b5-b2e1-7468a2e43396\",\"added_by\":\"auto\",\"created_at\":\"2026-04-30 09:03:47\",\"extension\":\"png\",\"order_by\":3,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":7157443,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"SFigure301.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-9355031/v1/f178d20c245ac214d9ef5250.png\"},{\"id\":108183938,\"identity\":\"e47f2e6b-61f3-457c-9bb9-0f71f7e94628\",\"added_by\":\"auto\",\"created_at\":\"2026-04-30 09:03:02\",\"extension\":\"pdf\",\"order_by\":4,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":7318232,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"Wb.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-9355031/v1/77b2424d6d7fc14959a71fa9.pdf\"},{\"id\":108183535,\"identity\":\"a0b53ee5-de5a-4575-b249-ce5afe500246\",\"added_by\":\"auto\",\"created_at\":\"2026-04-30 09:01:58\",\"extension\":\"docx\",\"order_by\":5,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":13480,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"Figurelegends.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-9355031/v1/3252393834bf3f2660321066.docx\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Cordycepin Enhances Paclitaxel Sensitivity in TNBC by Targeting the HIF-1α/RAD51 DNA Repair Feedback Loop\",\"fulltext\":[],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":false,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":true,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":true,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"npj-precision-oncology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"npjprecisiononcology\",\"sideBox\":\"Learn more about [npj Precision Oncology](http://www.nature.com/npjprecisiononcology/)\",\"snPcode\":\"41698\",\"submissionUrl\":\"https://submission.springernature.com/new-submission/41698/3\",\"title\":\"npj Precision Oncology\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"stoa\",\"reportingPortfolio\":\"NPJ\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Cordycepin, paclitaxel, triple-negative breast cancer, HIF-1α/RAD51, DNA repair, Chemotherapy sensitivity\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-9355031/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-9355031/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"Triple-negative breast cancer (TNBC) remains a serious global health burden for women, with an increasing incidence and a longstanding lack of effective therapeutic strategies. These unmet clinical needs highlight the urgent need to develop novel chemosensitizers and elucidate their underlying molecular mechanisms. Cordycepin(a natural bioactive compound) has been previously reported to exert synergistic anti-tumor effects in various malignant tumors. The present study aims to clarify the chemosensitizing mechanism of cordycepin in TNBC, which is characterized by high invasiveness and strong adaptability to hypoxia. Our results demonstrated that cordycepin significantly enhanced the cytotoxicity of paclitaxel in TNBC cells by inhibiting the HIF-1α/RAD51 positive feedback loop, a key driver of TNBC progression, thereby blocking DNA repair. These findings uncover a novel mechanistic role of cordycepin in enhancing chemosensitivity, providing a promising therapeutic strategy for improving clinical outcomes in patients with TNBC.\",\"manuscriptTitle\":\"Cordycepin Enhances Paclitaxel Sensitivity in TNBC by Targeting the HIF-1α/RAD51 DNA Repair Feedback Loop\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2026-04-29 19:51:19\",\"doi\":\"10.21203/rs.3.rs-9355031/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2026-04-21T08:22:19+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2026-04-20T02:07:07+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2026-04-13T04:56:40+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"npj Precision Oncology\",\"date\":\"2026-04-08T09:30:00+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"npj-precision-oncology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"npjprecisiononcology\",\"sideBox\":\"Learn more about [npj Precision Oncology](http://www.nature.com/npjprecisiononcology/)\",\"snPcode\":\"41698\",\"submissionUrl\":\"https://submission.springernature.com/new-submission/41698/3\",\"title\":\"npj Precision Oncology\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"stoa\",\"reportingPortfolio\":\"NPJ\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"174ad21b-7263-4fd8-b9ac-8572596d8695\",\"owner\":[],\"postedDate\":\"April 29th, 2026\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"under-review\",\"subjectAreas\":[{\"id\":66712590,\"name\":\"Biological sciences/Cancer\"},{\"id\":66712591,\"name\":\"Biological sciences/Drug discovery\"},{\"id\":66712592,\"name\":\"Health sciences/Oncology\"}],\"tags\":[],\"updatedAt\":\"2026-04-29T19:51:20+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2026-04-29 19:51:19\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-9355031\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-9355031\",\"identity\":\"rs-9355031\",\"version\":[\"v1\"]},\"buildId\":\"XKTyCvWXoU3ODBz1xrDgd\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}