DOI: 10.3724/SP.J.1249.2018.04339

Journal of Shenzhen University Science and Engineering (深圳大学学报理工版) 2018/35:4 PP.339-344

Reverse effect of chidamide on endocrine resistance in estrogen receptor-positive breast cancer

Endocrine therapy is the mainstay of treatment for estrogen receptor-positive breast cancer, but the occurrence of drug resistance limits its application. The aim of this study is to explore if chidamide, a histone deacetylase inhibitor, can be used for reversing endocrine resistance in estrogen receptor-positive breast cancer. MTS cell proliferation assay shows that monotherapy with 4-hydroxytamoxifen and chidamide have certain inhibitory effects on the proliferation of MCF-7 (estrogen receptor-positive breast cancer cell line), and additive effects upon combination. Epidermal growth factor induces resistance of MCF-7 to 4-hydroxytamoxifen, while chidamide can reverse this resistance. Western blotting shows that phosphorylation of MEK, ERK, AKT induced by epidermal growth factor can be reduced by chidamide, as well as the phosphorylation of estrogen receptor. In vivo efficacy in orthotopic transplantation breast tumor models also indicate that the effect of combination of chidamide and fulvestrant is more visible as compared with monotherapy. These findings suggest that chidamide can reverse endocrine resistance induced by epidermal growth factor in estrogen receptor positive breast cancer cells, and this reverse effect may be related to its inhibition of the pathways downstream of the epidermal growth factor and the pathway of activation of estrogen receptor.

Key words:pharmacology,breast cancer,chidamide,endocrine therapy,tamoxifen,fulvestrant,epidermal growth factor

ReleaseDate:2018-07-26 10:51:02

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