Chidamide enhances cytotoxicity of doxorubicin by promoting autophagy and apoptosis in breast cancer

Abstract

BackgroundBreast cancer (BC) is a prevalent disease that harms women's health, and in-depth investigations of the pathogenesis, treatment, and prevention of BC are the focus of many research programs. Chidamide (CHI) is a histone deacetylase suppressor that depresses histone deacetylase functions, thereby influencing cell growth through an epigenetic mechanism. However, CHI effects upon BC are largely unknown. Present research aimed to confirm the possibility of using CHI combined with chemotherapy drug doxorubicin (DOX) to prevent chemotherapeutic BC resistance in vivo and in vitro.MethodsIn this study, CCK8 (a plate colony formation assay) was applied to detect cell proliferation. Flow cytometry detection showed the apoptotic cell death of both T47D and MCF-7 cells. Nude mouse xenografts were used to detect tumor growth and pulmonary metastasis. High-throughput sequencing was used to detect expression of different genes.ResultsOur data showed that CHI treatment reduced BC cell proliferation, tumor growth, and cell invasion. CHI treatments stimulated BC cell apoptosis by promoting ULK2-mediated autophagy and increasing MCF-7 cell sensitivity to DOX, resulting in decreased tumor growth.ConclusionCollectively, our results illustrated that CHI enhanced DOX cytotoxicity by promoting apoptosis and autophagy in BC cells, which advised that CHI could be a candidate drug for BC patient treatments.