Corilagin increases the sensitivity of neuroblastoma to cisplatin by regulating the PI3K/AKT signaling pathway

Corilagin increases the sensitivity of neuroblastoma to cisplatin by regulating the PI3K/AKT signaling pathway | 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 Corilagin increases the sensitivity of neuroblastoma to cisplatin by regulating the PI3K/AKT signaling pathway tingting lu, xinqiang zhu, xiaorong su, daorong hou, liang qin This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8731803/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Drug resistance remains the leading cause of cisplatin treatment failure in neuroblastoma (NB). This study aimed to investigate the potential of corilagin as an adjuvant therapy for overcoming cisplatin resistance in NB. In vitro functional assays—including cell viability (CCK-8), colony formation, transwell migration, and invasion assays—were conducted to evaluate the effects of corilagin in combination with cisplatin on human NB cell lines (SH-SY5Y and SK-N-BE(2)) and a cisplatin-resistant subline (SH-SY5Y/R). In vivo tumorigenesis experiments were performed to assess the suppressive effects of the corilagin-cisplatin combination on tumor growth initiated by SH-SY5Y and SH-SY5Y/R cells in mouse models. RNA sequencing was utilized to identify molecular mechanisms associated with cisplatin resistance and the therapeutic action of corilagin, followed by functional validation using 740Y-P, a specific agonist of the PI3K/AKT pathway. Our results showed that the combination of corilagin and cisplatin significantly inhibited proliferation, migration, invasion, and autophagic activity in SH-SY5Y/R cells, while robustly inducing apoptosis. Importantly, the PI3K/AKT signaling pathway was found to be hyperactivated during the development of cisplatin resistance, whereas corilagin effectively suppressed this activation. These findings indicate that corilagin enhances cisplatin sensitivity in NB cells through modulation of the PI3K/AKT signaling pathway. Biological sciences/Cancer Biological sciences/Cell biology Health sciences/Oncology corilagin neuroblastoma drug sensitivity PI3K/AKT chemotherapy Full Text Additional Declarations No competing interests reported. Supplementary Files SI2026.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 24 Apr, 2026 Reviews received at journal 23 Feb, 2026 Reviewers agreed at journal 11 Feb, 2026 Reviewers agreed at journal 10 Feb, 2026 Reviewers invited by journal 08 Feb, 2026 Editor assigned by journal 08 Feb, 2026 Editor invited by journal 06 Feb, 2026 Submission checks completed at journal 04 Feb, 2026 First submitted to journal 04 Feb, 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. 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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-8731803","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":589080408,"identity":"6555f018-3af8-4b68-8c17-78d398535c5c","order_by":0,"name":"tingting lu","email":"","orcid":"","institution":"Jiangsu Provincial Hospital of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"tingting","middleName":"","lastName":"lu","suffix":""},{"id":589080409,"identity":"e581ffc0-7ee9-4c1c-a260-3a95e7404f63","order_by":1,"name":"xinqiang zhu","email":"","orcid":"","institution":"Jiangsu Provincial Hospital of Traditional 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