FigsharePub Date : 1753-01-01DOI: 10.1021/acsami.2c15143.s001
Mengjun Zhang (9196553), Haodi Yue (12749984), Xin Huang (11077), Jialin Wang (490082), Zengbei Li (13985040), Xinjie Deng (12562468)
{"title":"NovelnPlatinum NanoclustersnActivate PI3K/AKT/mTORnSignaling Pathway-Mediated Autophagy for Cisplatin-Resistant OvariannCancer Therapy","authors":"Mengjun Zhang (9196553), Haodi Yue (12749984), Xin Huang (11077), Jialin Wang (490082), Zengbei Li (13985040), Xinjie Deng (12562468)","doi":"10.1021/acsami.2c15143.s001","DOIUrl":"https://doi.org/10.1021/acsami.2c15143.s001","url":null,"abstract":"Platinum (Pt)-based chemotherapyndrugs such as cisplatinnare thenfirst line and core options for the treatment of ovarian cancer (OC),nwhile cisplatin resistance has a worse prognosis and low 5 year survivalnrate for patients. Chemotherapeutic drugs synthesized from nanomaterialsnhave shown great potential in biomedicine; however, research intontheir application for OC resistance is rarely discussed. This studynis proposed to elucidate the anti-tumor effects of polyethyleniminen(PEI)-caged platinum nanoclusters (Pt NCs) on cisplatin-resistantnOC. The results of confocal microscopy showed that Pt NCs enteredncisplatin-resistant OC cells dose-dependently and aggregated bothnin the cytoplasm and inside the nucleus. Subsequently, according tonthe results of CCK8 assay, wound healing assay, clone formation assay,nTranswell assay, Ki-67 immunofluorescence assay, and flow cytometrynassay, the proliferation and migration of cisplatin-resistant OC cellsnwere inhibited by Pt NCs, as well as their apoptosis was promoted.nIn addition, we validated the anti-tumor effect of Pt NCs on regulatingnautophagy via monodansylcadaverine (MDC) staining, transmission electronnmicroscopy observation of the autophagic ultrastructure, LC3-II-GFPnand P62-GFP adenovirus single-label immunofluorescence, and westernnblotting; meanwhile, the role of Pt NCs in adjusting autophagy throughnmodulation of the PI3K-AKT-mTOR signaling was verified. Based on thesenresults, it appears that cisplatin-resistant OC cells can undergonapoptosis when Pt NCs activate autophagy by inhibiting the PI3K/AKT/mTORnpathway, exhibiting a promising potential of Pt NCs in the developmentnof a novel chemotherapeutic agent for patients suffering from cisplatin-resistantnOC.","PeriodicalId":523600,"journal":{"name":"Figshare","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"1753-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147918848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}