Chidamide enhances inhibitory effect on colon cancer cells by modulating tumorassociated macrophage
10.3872/j.issn.1007-385x.2019.04.003
- VernacularTitle:西达本胺通过调控肿瘤相关巨噬细胞功能增强对结肠癌细胞的抑制作用
- Author:
GAO Yang
1
;
HUO Miaomiao
1
;
LIU Mei
1
;
XU Ningzhi
1
;
ZHU Hongxia
1
Author Information
1. Laboratory of Cell and Molecular Biology/State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
- Publication Type:Journal Article
- Keywords:
colon cancer;
CT26 cell;
chidamide;
histone deacetylase (HDAC);
tumor-associated macrophages (TAM)
- From:
Chinese Journal of Cancer Biotherapy
2019;26(4):381-388
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the effect of tumor-associated macrophage (TAM) on the anti-tumor function of chidamide and to explore the mechanism. Methods: Mouse macrophage cell linesAna1 and Raw264.7 were cultured in vitro and induced into TAM with tumor supernatant. HDAC enzyme activity was detected after TAM treated with chidamide. The mRNA expressions of cytokines, such as IL-6, IL-12,TNF and IL-1β, in TAM were detected by qPCR. The protein expression of NF-κB and STAT3 in TAM treated with chidamide were detected by Wb. The mixture of TAM and colon cancer CT26 cells was inoculated into nude mice to construct the subcutaneous xenograft model; and the efficacy of chidamide (3.87 mg/kg) on the growth of CT26 xenograft tumors was observed. The protein expressions of PCNA, F4/80, Arg1 and iNos were detected by immunohistochemistry. Results: Chidamide inhibited the proliferation of CT26 cells. In the in vivo experiment, the inhibition rate of chidamide alone on CT26 xenograft was about 18.7%; however, the inhibition rate was up to 57.2% with the presence of TAM. Chidamide could inhibit the activity of HDAC enzyme in TAM, and further increase the Histone acetylation level. Chidamide could affect the expression of nuclear transcription factor NF-κB, inhibit the expressions of Arg1, IL-6 and IL-12, but up-regulate the expressions of iNOS, TNF and IL-1β in TAM. Conclusion: Chidamide can enhance its inhibitory effect on colon cancer CT26 cells via regulating the expression of cytokines and inhibiting the activity of HDAC in TAM.
- Full text:20190403.pdf
