J Cancer 2021; 12(20):6198-6208. doi:10.7150/jca.61602 This issue

Research Paper

Chidamide, a subtype-selective histone deacetylase inhibitor, enhances Bortezomib effects in multiple myeloma therapy

Yanjuan He1, Duanfeng Jiang2, Kaixuan Zhang1, Yinghong Zhu3, Jingyu Zhang3, Xuan Wu3, Jiliang Xia3, Yan Zhu1, Lang Zou1, Jian Hu1, Yajuan Cui4, Wen Zhou3, Fangping Chen1✉

1. Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
2. Department of Hematology, The 3rd Xiangya Hospital, Central South University, Changsha, China.
3. Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, China.
4. Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, China.

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Citation:
He Y, Jiang D, Zhang K, Zhu Y, Zhang J, Wu X, Xia J, Zhu Y, Zou L, Hu J, Cui Y, Zhou W, Chen F. Chidamide, a subtype-selective histone deacetylase inhibitor, enhances Bortezomib effects in multiple myeloma therapy. J Cancer 2021; 12(20):6198-6208. doi:10.7150/jca.61602. Available from https://www.jcancer.org/v12p6198.htm

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Abstract

Graphic abstract

Drug resistance is the major cause for disease relapse and patient death in multiple myeloma (MM). It is an urgent need to develop new therapies to overcome drug resistance in MM. Chidamide (CHI), a novel oral HDAC inhibitor targeting HDAC1, 2, 3 and 10, has shown potential therapeutic effect in MM. In this study, we determined that CHI exhibited significant anti-tumor effect on MM cells both in vitro and in vivo, which was positively correlated with the expression of HDAC1. Meanwhile, CHI enhanced Bortezomib (BTZ) effects synergistically in MM cells and a combination of CHI with BTZ induced myeloma cell apoptosis and G0/G1 arrest in vitro and in vivo. Mechanistically, the synergistic anti-tumor effect of CHI and BTZ was related with the increased production of reactive oxygen species (ROS) dependent DNA damage and the changes of cell apoptosis and cycle pathways. Our data indicate that CHI may be a suitable drug to sensitize BTZ in MM cells, which provides novel insight into the therapy for MM patients.

Keywords: Multiple myeloma, Chidamide, Bortezomib, Reactive oxygen species