Inhibition of TFF3 Enhances Sensitivity-and Overcomes Acquired Resistance-to Doxorubicin in Estrogen Receptor-Positive Mammary Carcinoma.

ABSTRACT: Dose-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 part

SUBMITTER: Poh HM 

PROVIDER: S-EPMC6826976 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature