{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T01:15:34Z","timestamp":1769562934440,"version":"3.49.0"},"reference-count":56,"publisher":"American Association for the Advancement of Science (AAAS)","content-domain":{"domain":["spj.science.org"],"crossmark-restriction":true},"short-container-title":["Research"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:p>\n            Platinum-based chemotherapy remains the main systemic treatment of ovarian cancer (OC). However, the inevitable development of platinum and poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) resistance is associated with poor outcomes, which becomes a major obstacle in the management of this disease. The present study developed \u201call-in-one\u201d nanoparticles that contained the PARPi olaparib and gallium (Ga) (III) (olaparib-Ga) to effectively reverse PARPi resistance in platinum-resistant A2780-cis and SKOV3-cis OC cells and in SKOV3-cis tumor models. Notably, the olaparib-Ga suppressed SKOV3-cis tumor growth with negligible toxicity. Moreover, the suppression effect was more evident when combining olaparib-Ga with cisplatin or carboplatin, as evaluated in A2780-cis and SKOV3-cis cells. Mechanistically, the combined treatment induced DNA damage, which elicited the activation of ataxia telangiectasia mutated (ATM)\/AMT- and Rad3-related (ATR) checkpoint kinase 1 (Chk1)\/Chk2 signal transduction pathways. This led to the arrest of cell cycle progression at S and G\n            <jats:sub>2<\/jats:sub>\n            \/M phases, which eventually resulted in apoptosis and cell death due to unrepairable DNA damage. In addition, effective therapeutic responses to olaparib-Ga and cisplatin combination or olaparib-Ga and carboplatin combination were observed in SKOV3-cis tumor-bearing animal models. Altogether, the present findings demonstrate that olaparib-Ga has therapeutic implications in platinum-resistant OC cells, and the combination of olaparib-Ga with cisplatin or carboplatin may be promising for treating patients with OC who exhibit resistance to both PARPi and platinum.\n          <\/jats:p>","DOI":"10.34133\/research.0070","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T15:15:23Z","timestamp":1674227723000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":14,"title":["Nanoengineered Gallium Ion Incorporated Formulation for Safe and Efficient Reversal of PARP Inhibition and Platinum Resistance in Ovarian Cancer"],"prefix":"10.34133","volume":"6","author":[{"given":"Yangyang","family":"Li","sequence":"first","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixuan","family":"Cen","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Women\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengyan","family":"Tu","sequence":"additional","affiliation":[{"name":"Women\u2019s Reproductive Health Laboratory of Zhejiang Province, Women\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenzhen","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Women\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sangsang","family":"Tang","sequence":"additional","affiliation":[{"name":"Women\u2019s Reproductive Health Laboratory of Zhejiang Province, Women\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiguo","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Women\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, China."},{"name":"Women\u2019s Reproductive Health Laboratory of Zhejiang Province, Women\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, China."},{"name":"Cancer Center, Zhejiang University, Hangzhou 310058, Zhejiang, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Laboratory, \u00c5bo Akademi University, Turku FI-20520, Finland."},{"name":"Turku Bioscience Centre, University of Turku and \u00c5bo Akademi University, Turku FI-20520, Finland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junfen","family":"Xu","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China."},{"name":"Department of Gynecologic Oncology, Women\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","reference":[{"issue":"4","key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/ijc.33588","article-title":"Cancer statistics for the year 2020: An overview","volume":"149","author":"Ferlay J","year":"2021","unstructured":"Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Pi\u00f1eros M, Znaor A, Bray F. 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