Chidamide inhibits the growth of cholangiocarcinoma cells, according to a new study published in Stem Cells International. Treatment with chidamide reduced the proliferation, migration, and invasion of 2 different CCA cell lines (QBC939 and SNU308). 

Apoptosis and autophagy of CCA cells were also promoted in a dose-dependent fashion through treatment with chidamide. Chidamide, a novel inhibitor of histone deacetylase (HDAC), appears to work through the reduction of HDAC3 expression. HDAC3 was found to be significantly increased in CCA compared to normal bile duct tissue and is associated with a poor prognosis in patients.

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The inhibition of HDAC3 was also found to increase acetylation of forkhead box protein O1 (FOXO1). Previous trials have reported that FOXO1 regulates autophagy in tumor cells and that its acetylation increases autophagy levels.

“[Chidamide] suppresses HDAC3 expression and induces acetylation of FOXO1, thus impeding the proliferation, migration, and invasion of CCA cells, while promoting cell apoptosis and autophagy, ultimately arresting the growth of CCA,” the authors said.

Treatment with chidamide also exhibited antitumor properties in an in vivo nude mouse model where the mice were injected with human CCA QBC939 cells. The growth of the xenografted tumors was inhibited in the mice in a dose-dependent fashion. Histology revealed that the tumors treated with chidamide had reduced numbers of CCA cells, which were replaced with fibrous tissue.

Further analysis of the tumor tissue also revealed that the cells displayed lower HDAC3 levels and an increase in FOXO1 acetylation in a dose-dependent manner.

“This study demonstrates that [chidamide] has a significant tumor suppressing effect on CCA and may eventually provide a new treatment approach for CCA. We propose that [chidamide] may act synergistically with other chemotherapy drugs in the treatment of CCA,” the authors wrote.

Screening of HDAC expression levels in The Cancer Genome Atlas (TCGA) database revealed that in addition to HDAC3, the levels of HDAC7, HDAC10, and HDAC11 were also elevated in CCA samples compared to normal cells.

Reference

Li Y, Zheng J, Huo Q, Chen Z, Chen J, Xu X. Chidamide suppresses the growth of cholangiocarcinoma by inhibiting HDAC3 and promoting FOXO1 acetylation. Stem Cells Int. 2022;2022:3632549. doi:10.1155/2022/3632549