{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T06:43:18Z","timestamp":1785825798058,"version":"3.56.0"},"reference-count":83,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cisplatin is one of the most effective chemotherapeutic agents used in the treatment of ovarian cancer. However, the frequent development of cisplatin resistance remains a significant limitation, leading to therapeutic failure and poor patient outcomes. Cisplatin cytotoxicity is attributed to the generation of toxic DNA lesions, which can be recognized and processed by a variety of proteins, including the high mobility group box 1 (HMGB1) protein. HMGB1 is a multifunctional protein, which is involved in chromatin remodeling and multiple DNA damage repair pathways. In this study, we investigated the role of HMGB1 in modulating cisplatin sensitivity in human ovarian cancer cells. Using cisplatin\u2010sensitive and cisplatin\u2010resistant human ovarian cancer cell lines, we employed siRNA\u2010mediated HMGB1 knockdown to assess its impact on the cellular responses to cisplatin treatment. In clonogenic survival assays, HMGB1 depletion resulted in a significant reduction in colony formation in cisplatin\u2010resistant cells upon cisplatin exposure, compared with nontargeting siRNA treated cells. Additionally, HMGB1 inhibition significantly enhanced cisplatin\u2010induced apoptosis in the cisplatin\u2010resistant cells. Mechanistically, HMGB1\u2010depleted cells exhibited altered DNA damage responses via modulation of ATM\/CHK2 and ATR\/CHK1 activity following cisplatin treatment. Notably, DNA immunoblot and modified alkaline comet assay results demonstrated that HMGB1 depletion stimulated cisplatin\u2010DNA adduct formation and impaired the removal of cisplatin\u2010DNA adducts, particularly in the cisplatin\u2010resistant cells. Collectively, these findings uncover novel functions of HMGB1 in mediating cisplatin sensitivity, emphasizing its potential as a therapeutic target to overcome cisplatin resistance in ovarian cancer.<\/jats:p>","DOI":"10.1002\/mc.70074","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T11:46:57Z","timestamp":1767959217000},"page":"375-390","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["HMGB1 Assists in Overcoming Cisplatin Resistance in Chemoresistant Human Ovarian Cancer Cells"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0346-4452","authenticated-orcid":false,"given":"Van","family":"Huynh","sequence":"first","affiliation":[{"name":"Division of Pharmacology and Toxicology, College of Pharmacy The University of Texas at Austin, Dell Pediatric Research Institute Austin Texas 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