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dc.contributor.authorMa, H.
dc.contributor.authorYan, D.
dc.contributor.authorWang, Y.
dc.date.accessioned2019-03-29T14:47:38Z
dc.date.available2019-03-29T14:47:38Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85062394376&doi=10.1111%2fcas.13940&partnerID=40&md5=bf03e25d8222cf58ddaca8fcbeb21aec
dc.identifier.urihttp://hdl.handle.net/10713/8716
dc.description.abstractThe interleukin (IL)-6/glycoprotein (GP)130/signal transducer and activator of transcription (STAT)3 pathway is emerging as a target for the treatment of hepatocellular carcinoma. IL-6 binds to IL-6R, forming a binary complex, which further combines with GP130 to transduce extracellular signaling by activating STAT3. Therefore, blocking the interaction between IL-6 and GP130 may inhibit the IL-6/GP130/STAT3 signaling pathway and its biological effects. It has been reported that bazedoxifene acetate (BAZ), a selective estrogen receptor modulator approved by the US Food and Drug Administration, could inhibit IL-6/GP130 protein-protein interactions. Western blot, immunofluorescence staining, wound healing and colony formation assays were used to detect the effect of BAZ on liver cancer cells. Cell viability was evaluated by MTT assay. Apoptosis of cells was determined using the Annexin V-FITC detection kit. Mouse xenograft tumor models were utilized to evaluate the effect of BAZ in vivo. Our data showed that BAZ inhibited STAT3 phosphorylation (P-STAT3) and expression of STAT3 downstream genes, inducing apoptosis in liver cancer cells. BAZ inhibited P-STAT3 induced by IL-6, but not by leukemia inhibitory factor. BAZ inhibited P-STAT1 and P-STAT6 less significantly as elicited by interferon-α, interferon-γ and IL-4. In addition, pretreatment of BAZ impeded the translocation of STAT3 to nuclei induced by IL-6. BAZ inhibited cell viability, wound healing and colony formation in vitro. Furthermore, tumor growth in HEPG2 mouse xenografts were significantly inhibited by daily intragastric gavage of BAZ. Our results suggest that BAZ inhibited the growth of hepatocellular carcinoma in vitro and in vivo, indicating another potential strategy for HCC prevention and therapy. ©2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.en_US
dc.description.sponsorshipThis work was supported by the National Natural Science Foundation of China to L.L. (no. 81372402, 81001005, 81570416) and S.L. (no. 81570337), and the Outstanding Young Investigator Foundation of Tongji Hospital (no. YXQN009) and the Fundamental Research Fund of HUST (no. 0118540019) to L.L.en_US
dc.description.urihttps://dx.doi.org/10.1111/cas.13940en_US
dc.language.isoen_USen_US
dc.publisherBlackwell Publishing Ltden_US
dc.relation.ispartofCancer Science
dc.subjectbazedoxifeneen_US
dc.subjectglycoprotein 130en_US
dc.subjectsignal transducer and activator of transcription 3en_US
dc.subject.meshCarcinoma, Hepatocellularen_US
dc.subject.meshInterleukin-6en_US
dc.titleBazedoxifene exhibits growth suppressive activity by targeting interleukin-6/glycoprotein 130/signal transducer and activator of transcription 3 signaling in hepatocellular carcinomaen_US
dc.typeArticleen_US
dc.identifier.doi10.1111/cas.13940
dc.identifier.pmid30648776


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