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dc.contributor.authorWinship, A
dc.contributor.authorVan Sinderen, M
dc.contributor.authorRainczuk, K
dc.contributor.authorDimitriadis, E
dc.date.accessioned2020-12-10T01:52:42Z
dc.date.available2020-12-10T01:52:42Z
dc.date.issued2017-04-04
dc.identifierpii: 15187
dc.identifier.citationWinship, A., Van Sinderen, M., Rainczuk, K. & Dimitriadis, E. (2017). Therapeutically blocking Interleukin-11 Receptor-a enhances doxorubicin cytotoxicity in high grade type I endometrioid tumours. ONCOTARGET, 8 (14), pp.22716-22729. https://doi.org/10.18632/oncotarget.15187.
dc.identifier.issn1949-2553
dc.identifier.urihttp://hdl.handle.net/11343/253825
dc.description.abstractHigh grade type I endometrial cancers have poor prognosis. Interleukin (IL)11 is elevated in tumours and uterine lavage with increasing tumour grade in women. IL11 regulates cell cycle, invasion and migration and we recently demonstrated that IL11 receptor (R)α inhibition impaired low and moderate grade endometrial tumourigenesis in vivo. In this report, we hypothesized that micro-RNA(miR)-1 regulates IL11 and that IL11 promotes high grade endometrial tumour growth. We aimed to determine whether combination treatment using an anti-human IL11Rα blocking antibody (Ab) and doxorubicin chemotherapeutic impairs high grade tumour growth. MiR-1 was absent in human endometrial tumours versus human benign endometrium (n = 10/group). Transfection with miR-1 mimic restored miR-1 expression, down-regulated IL11 mRNA and impaired cell viability in grade 3-derived AN3CA human endometrial epithelial cancer cells. AN3CA cell proliferation was reduced in response to Ab and doxorubicin combination treatment versus Ab, IgG control, or doxorubicin alone. Subcutaneous xenograft tumours were established in female Balb/c athymic nude mice using AN3CA cells expressing IL11 and IL11Rα. Administration of recombinant human IL11 to mice (n = 4/group) activated IL11 downstream target, signal transducers and activators of transcription (STAT3) and significantly increased tumour growth (p < 0.05), suggesting that IL11 promotes high grade tumour growth. IL11Rα blocking Ab reduced STAT3 phosphorylation and combination treatment with doxorubicin resulted in a significant reduction in tumour growth (p < 0.05) compared to Ab, doxorubicin, or IgG control. Our data suggest that therapeutically targeting IL11Rα in combination with doxorubicin chemotherapy could inhibit high grade type I endometrioid cancer growth.
dc.languageEnglish
dc.publisherIMPACT JOURNALS LLC
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleTherapeutically blocking Interleukin-11 Receptor-a enhances doxorubicin cytotoxicity in high grade type I endometrioid tumours
dc.typeJournal Article
dc.identifier.doi10.18632/oncotarget.15187
melbourne.affiliation.departmentObstetrics and Gynaecology
melbourne.source.titleOncotarget
melbourne.source.volume8
melbourne.source.issue14
melbourne.source.pages22716-22729
dc.rights.licenseCC BY
melbourne.elementsid1358160
melbourne.contributor.authorDimitriadis, Evdokia
dc.identifier.eissn1949-2553
melbourne.accessrightsOpen Access


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