SUN-LB054 Cilengitide Reverts Thyroid Hormones Effects in Bexarotene Treatment of Breast Cancer Cells

Abstract

Bexarotene (Bex) is an oral retinoid-X-receptor agonist that is effective for the treatment of early and advanced-stage in cutaneous T cell lymphoma. There are ongoing clinical trials to determine its role in both breast cancer treatment and prevention. Unfortunately, hypothyroidism is recognized as an important side effect of such therapy, potentially manageable by thyroid hormones (THs) co-administration. We previously found (1) that physiological levels of THs increased cell proliferation of different subtypes of human T cell lymphoma by activating both the nuclear (TR) and membrane (integrin αVβ3) THs receptors. We first demonstrated that MDA-MB-231 triple negative breast cancer cells expressed both TR and integrin αvβ3 dimer. Also, we found that THs induced MDA-MB-231 cell proliferation (p<0.01; n=4). Interestingly, in THs-depleted culture conditions we observed a higher effect of Bex in decreasing cell viability (p<0.05; n=3) and THs impaired the action of this drug (p<0.05; n=3). Then, we performed the same experiments with THs and Bex in presence of the inhibitor of the non-canonical THs membrane receptor integrin αVβ3, cilengitide. We found that pharmacological inhibition with cilengitide improved the TH effect on Bex activity (p<0.01; n=3) in MDA-MB-231 cells, indicating that integrin αVβ3 plays a key role in THs-induced MDA-MB-231 cell proliferation. Our data suggest that the requirement of THs replacement therapy may counteract Bex antitumor effect but concomitant administration with cilengitide could be an effective strategy to improve Bex treatment in breast cancer. Reference: (1) Cayrol et al, Blood 2015 Jan 29;125(5):841-851. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.