The combination of the HDAC1 inhibitor SAHA and doxorubicin has synergic efficacy in triple negative breast cancer in vivo

Yuheng Pang; Runze Shi; Liujia Chan; Yu Lu; Di Zhu; Tong Liu; Meisi Yan; Yuji Wang; Wenjing Wang

doi:10.1016/j.phrs.2023.106926

The combination of the HDAC1 inhibitor SAHA and doxorubicin has synergic efficacy in triple negative breast cancer in vivo

Pharmacol Res. 2023 Oct:196:106926. doi: 10.1016/j.phrs.2023.106926. Epub 2023 Sep 15.

Authors

Yuheng Pang¹, Runze Shi², Liujia Chan³, Yu Lu³, Di Zhu³, Tong Liu¹, Meisi Yan⁴, Yuji Wang⁵, Wenjing Wang⁶

Affiliations

¹ Department of Breast Surgery, Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang, PR China; NHC Key Laboratory of Cell Transplantation, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, PR China.
² Department of Breast Surgery, Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang, PR China.
³ College of Pharmaceutical Sciences, Capital Medical University, Beijing, PR China.
⁴ Pathology Teaching and Research Section, Basic Medical College of Harbin Medical University, Harbin, Heilongjiang, PR China; NHC Key Laboratory of Cell Transplantation, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, PR China. Electronic address: msyan@hrbmu.edu.cn.
⁵ College of Pharmaceutical Sciences, Capital Medical University, Beijing, PR China. Electronic address: wangyuji@ccmu.edu.cn.
⁶ Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing, PR China. Electronic address: wangwenjing85321@ccmu.edu.cn.

PMID: 37716547
DOI: 10.1016/j.phrs.2023.106926

Abstract

Vorinostat (SAHA) is a histone deacetylase inhibitor that exerts its effects through epigenetic regulation. Specifically, SAHA can inhibit the proliferation of triple-negative breast cancer (TNBC) cells alone or in combination with other chemotherapeutic agents. Doxorubicin (DOX), a traditional chemotherapeutic drug, exhibits a potent cytotoxic effect on cancer cells while also inducing strong toxic effects. In this study, we investigated the synergistic potential of these two drugs in combination against TNBC. Our results suggested that the combination of these two drugs could enhance the inhibitory effect on cancer cell proliferation, resulting in alterations in cell mitotic phase, and suppression of cancer cell stemness. Moreover, our in vivo study unveiled that when SAHA was combined with DOX, it not only exhibited an inhibitory effect on tumor metastasis but also played a role in regulating the immune microenvironment within tumors. Overall, the combination of DOX and SAHA presents a promising avenue for innovative combination chemotherapy in the context of TNBC.

Keywords: Cancer stem cells; Doxorubicin; Triple negative breast cancer; Tumor immune microenvironment; Vorinostat.