Please use this identifier to cite or link to this item: https://doi.org/10.3390/cancers11101528
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dc.titleInhibition of TFF3 enhances sensitivity—and overcomes acquired resistance—to doxorubicin in estrogen receptor-positive mammary carcinoma
dc.contributor.authorPoh, H.M.
dc.contributor.authorChiou, Y.S.
dc.contributor.authorChong, Q.Y.
dc.contributor.authorChen, R.-M.
dc.contributor.authorRangappa, K.S.
dc.contributor.authorMa, L.
dc.contributor.authorZhu, T.
dc.contributor.authorKumar, A.P.
dc.contributor.authorPandey, V.
dc.contributor.authorBasappa
dc.contributor.authorLee, S.-C.
dc.contributor.authorLobie, P.E.
dc.date.accessioned2021-12-06T04:22:31Z
dc.date.available2021-12-06T04:22:31Z
dc.date.issued2019
dc.identifier.citationPoh, H.M., Chiou, Y.S., Chong, Q.Y., Chen, R.-M., Rangappa, K.S., Ma, L., Zhu, T., Kumar, A.P., Pandey, V., Basappa, Lee, S.-C., Lobie, P.E. (2019). Inhibition of TFF3 enhances sensitivity—and overcomes acquired resistance—to doxorubicin in estrogen receptor-positive mammary carcinoma. Cancers 11 (10) : 1528. ScholarBank@NUS Repository. https://doi.org/10.3390/cancers11101528
dc.identifier.issn2072-6694
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/209544
dc.description.abstractDose-dependent toxicity and acquired resistance are two major challenges limiting the efficacious treatment of mammary carcinoma (MC) with doxorubicin. Herein, we investigated the function of Trefoil Factor 3 (TFF3) in the sensitivity and acquired resistance of estrogen receptor positive (ER+) MC cells to doxorubicin. Doxorubicin treatment of ER+MC cells increased TFF3 expression. The depletion of TFF3 by siRNA or inhibition with a small molecule TFF3 inhibitor (AMPC) synergistically enhanced the efficacy of doxorubicin in ER+MC through the suppression of doxorubicin-induced AKT activation and enhancement of doxorubicin-induced apoptosis. Elevated expression of TFF3 and increased activation of AKT were also observed using a model of acquired doxorubicin resistance in ER+MC cells. AMPC partially re-sensitized the doxorubicin resistant cells to doxorubicin-induced apoptosis. Indeed, doxorubicin resistant ER + MC cells exhibited increased sensitivity to AMPC as a single agent compared to doxorubicin sensitive cells. In vivo, AMPC attenuated growth of doxorubicin sensitive ER+MC xenografts whereas it produced regression of xenografts generated by doxorubicin resistant ER+MC cells. Hence, TFF3 inhibition may improve the efficacy and reduce required doses of doxorubicin in ER+MC. Moreover, inhibition of TFF3 may also be an effective therapeutic strategy to eradicate doxorubicin resistant ER+MC. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
dc.publisherMDPI AG
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceScopus OA2019
dc.subjectAcquired resistance
dc.subjectApoptosis
dc.subjectDose-dependent toxicity
dc.subjectDoxorubicin
dc.subjectMammary carcinoma
dc.subjectPI3K/AKT
dc.subjectTrefoil factor 3 (TFF3)
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentMEDICINE
dc.contributor.departmentINST OF MOLECULAR & CELL BIOLOGY
dc.description.doi10.3390/cancers11101528
dc.description.sourcetitleCancers
dc.description.volume11
dc.description.issue10
dc.description.page1528
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