Combination Therapy Based on FLIM-FRET Screening in ERα Breast Cancer
Abstract
Estrogen receptor (ER)-α positive breast cancers embodies the prevailing form of breast cancers. One of the main therapeutic methods is hormone therapy by selectively modulate ERα. Epigenetic regulations have been emerging as a powerful tool for cancer therapy. The selection of combination drug treatment of ER modulator with epigenetic treatment on ER positive breast cancer is not well tested or understood. We fast screened ER?’s interaction with multiple epigenetic markers with MCF7 cells in vitro as well as patient samples using immunostaining and FLIM-FRET. Based on screening result, we selectively target histone acetylation at H4K12 and H3K27 by histone acetyltransferase inhibitors (HATi). The effects of combination drug treatment of ER modulator tamoxifen with selective HATi-anacardic acid were tested in mice xenograft model. We observed that combination of tamoxifen and anacardic acid inhibits tumor growth in mice xenograft. Treatment of anacardic acid disrupts ER-histone acetylation interactions. The expression level of ERα related genes decreased in combination therapy compare with either drug alone. These data indicate that combination treatment of tamoxifen and anacardic acid inhibits tumor proliferation by reducing ERα-DNA/histone acetylation interaction and inhibits ERα-meditated transcriptions.
Degree
M.S.A.B.E.
Advisors
Irudayaraj, Purdue University.
Subject Area
Biomedical engineering
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