Show simple item record

dc.contributor.authorWei, J.
dc.contributor.authorMa, L.
dc.contributor.authorLai, Y.-H.
dc.date.accessioned2019-03-29T14:42:03Z
dc.date.available2019-03-29T14:42:03Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85061245895&doi=10.1186%2fs13046-019-1072-8&partnerID=40&md5=c1238a44ca17d456619115f45091f40a
dc.identifier.urihttp://hdl.handle.net/10713/8610
dc.descriptionCorrection: Bazedoxifene as a novel GP130 inhibitor for Colon Cancer therapy (Journal of Occupational Medicine and Toxicology (2019) 38 (63) DOI: 10.1186/s13046-019-1072-8)
dc.description.abstractBackground: Interleukin-11 (IL-11), a dominant IL-6 family cytokine, is involved in tumorigenesis, tumor progression and differentiation in colon cancer cells. IL-11 signaling has been recently identified as a potential therapeutic target in colon cancer. Bazedoxifene, a third- generation selective estrogen modulator approved by the Food and Drug Administration (FDA), is a novel inhibitor of IL-11/GP130 signaling discovered by docking modeling. Methods: In this study, the inhibition efficacy of bazedoxifene in colon cancer cells and its potential mechanism were investigated in vitro and in vivo by using MTT cell viability assay, BrdU cell proliferation assay, colony formation assay, wound-healing/cell migration assay, immunofluorescence, western blot assay and the mouse xenograft tumor model. Results: Bazedoxifene inhibits phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) and its nuclear translocation induced by IL-11 in colon cancer cells. It also inhibits p-STAT3 induced by IL-6 and IL-11 but not by OSM or STAT1 phosphorylation induced by INF-γ in human colon cancer cells. In addition, bazedoxifene can significantly inhibit phosphorylation of AKT and STAT3 downstream targets. Furthermore, bazedoxifene alone or together with oxaliplatin can significantly induce apoptosis, inhibit cell viability, cell colony formation and cell migration in colon cancer cells. Knock-down of IL-11R can reduce the sensitivity of colon cancer cells to bazedoxifene. IL-11 can reduce the efficacy of oxaliplatin-mediated inhibition of cell viability. Consistent with in vitro findings, bazedoxifene alone also attenuated HCT-15 xenograft tumor burden and reduced p-STAT3, p-AKT and p-ERK in vivo. Its combination with oxaliplatin attenuated DLD-1 xenograft tumor burden and reduced p-STAT3 in vivo. Conclusions: Taken together, these results support bazedoxifene as a novel and effective therapeutic agent targeting IL-11/GP130 signaling for human colorectal cancer therapy. © 2019 The Author(s).en_US
dc.description.sponsorshipThis work was supported by the University of Maryland School of Medicine and Comprehensive Cancer Center start up fund.en_US
dc.description.urihttps://dx.doi.org/10.1186/s13046-019-1072-8en_US
dc.description.urihttps://doi.org/10.1186/s13046-019-1381-y
dc.language.isoen_USen_US
dc.publisherBioMed Central Ltd.en_US
dc.relation.ispartofJournal of Experimental and Clinical Cancer Research
dc.subjectbazedoxifeneen_US
dc.subjectGP130en_US
dc.subjectIL-11en_US
dc.subjectSTAT3en_US
dc.subject.lcshColon (Anatomy)--Canceren_US
dc.subject.meshOxaliplatinen_US
dc.titleBazedoxifene as a novel GP130 inhibitor for Colon Cancer therapyen_US
dc.typeArticleen_US
dc.identifier.doi10.1186/s13046-019-1072-8
dc.identifier.pmid30736824


This item appears in the following Collection(s)

Show simple item record