Reference Detail

Ref Type

Journal Article

PMID

(25384499)

Authors

Zhao B, He T

Title

Chidamide, a histone deacetylase inhibitor, functions as a tumor inhibitor by modulating the ratio of Bax/Bcl-2 and P21 in pancreatic cancer.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Oncology reports	33	1	2015 Jan	304-10	Oncol Rep

URL

Abstract Text

Chidamide is a newly designed histone deacetylase (HDAC) inhibitor that has been applied in clinical trials. This study aimed to test the effect of Chidamide on proliferation and apoptosis in pancreatic cancer cell lines and in vivo tumors, as well as to determine the underlying mechanism. The PaTu8988 pancreatic tumor cell line either in culture or inoculated in nude mice were used to evaluate the antitumor characteristics of Chidamide. Proliferation and apoptosis of cultured PaTu8988 cells were examined by CCK-8 assay and Annexin V-FITC/PI double staining assay, respectively. Alterations in protein expression, including Caspase-3, Bcl-2‑like protein 4 (Bax), B-cell lymphoma 2 (Bcl-2) and p21, were tested by western blot analysis. The mRNA of different HDACs was examined by quantitative polymerase chain reaction (qPCR) experiments. Chidamide suppressed cell proliferation and induced early apoptosis of pancreatic tumor cells in a dose‑dependent manner after 48 h of treatment. Similarly, the in vivo study using pancreatic tumor murine model showed that Chidamide administration significantly inhibited the growth of pancreatic tumor and induced tumor cell apoptosis. The in vitro and in vivo studies found that Chidamide treatment significantly decreased the expression of type I HDACs, uncleaved Caspase-3 and p21 and increased the ratio of Bax/Bcl-2 expression. The results from the in vitro and in vivo studies suggested Chidamide might suppress the proliferation of pancreatic tumor cells by downregulating the expression of type I HDACs and p21, and promoting mitochondrial apoptosis pathway-dependent cell apoptosis in a dose-dependent manner. The study provided more evidence for clinical administration of Chidamide that targets pancreatic tumor cells and identified potential molecular targets for the development of potent anticancer drugs.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
Chidamide	Chidamide	0	0

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
Chidamide		CS055\|HBI-8000\|Epidaza\|Tucidinostat	HDAC Inhibitor 45	Chidamide (Tucidinostat) is an HDAC inhibitor, which may lead to increased apoptosis and decreased proliferation of tumor cells (PMID: 25384499, PMID: 32855355, PMID: 32801749).

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References