Show simple item record

dc.contributor.authorZhang, Ruijie
dc.contributor.authorYang, Xiaozhi
dc.contributor.authorRoque, Dana M
dc.contributor.authorLi, Chenglong
dc.contributor.authorLin, Jiayuh
dc.date.accessioned2021-05-07T15:04:48Z
dc.date.available2021-05-07T15:04:48Z
dc.date.issued2021-04-28
dc.identifier.urihttp://hdl.handle.net/10713/15599
dc.description.abstractOvarian cancer is the fifth most common cause of cancer deaths among American women. Platinum and taxane combination chemotherapy represents the first-line approach for ovarian cancer, but treatment success is often limited by chemoresistance. Therefore, it is necessary to find new drugs to sensitize ovarian cancer cells to chemotherapy. Persistent activation of Signal Transducer and Activator of Transcription 3 (STAT3) signaling plays an important role in oncogenesis. Using a novel approach called advanced multiple ligand simultaneous docking (AMLSD), we developed a novel nonpeptide small molecule, LLL12B, which targets the STAT3 pathway. In this study, LLL12B inhibited STAT3 phosphorylation (tyrosine 705) and the expression of its downstream targets, which are associated with cancer cell proliferation and survival. We showed that LLL12B also inhibits cell viability, migration, and proliferation in human ovarian cancer cells. LLL12B combined with either paclitaxel or with cisplatin demonstrated synergistic inhibitory effects relative to monotherapy in inhibiting cell viability and LLL12B-paclitaxel or LLL12B-cisplatin combination exhibited greater inhibitory effects than cisplatin-paclitaxel combination in ovarian cancer cells. Furthermore, LLL12B-paclitaxel or LLL12B-cisplatin combination showed more significant in inhibiting cell migration and growth than monotherapy in ovarian cancer cells. In summary, our results support the novel small molecule LLL12B as a potent STAT3 inhibitor in human ovarian cancer cells and suggest that LLL12B in combination with the current front-line chemotherapeutic drugs cisplatin and paclitaxel may represent a promising approach for ovarian cancer therapy.en_US
dc.description.urihttps://doi.org/10.1371/journal.pone.0240145en_US
dc.language.isoenen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.ispartofPLoS ONEen_US
dc.subjectchemoresistanceen_US
dc.subjectLLL12Ben_US
dc.subject.meshOvarian Neoplasms--drug therapyen_US
dc.subject.meshSTAT3 Transcription Factor--antagonists & Inhibitorsen_US
dc.titleA novel small molecule LLL12B inhibits STAT3 signaling and sensitizes ovarian cancer cell to paclitaxel and cisplatinen_US
dc.typeArticleen_US
dc.identifier.doi10.1371/journal.pone.0240145
dc.identifier.pmid33909625
dc.source.volume16
dc.source.issue4
dc.source.beginpagee0240145
dc.source.endpage
dc.source.countryUnited States


This item appears in the following Collection(s)

Show simple item record