BIX-01294 inhibits the proliferation of esophageal squamous cell carcinoma cells by inducing DNA damage and activating the mitochondrial apoptosis pathway
- VernacularTitle:BIX-01294 通过诱导 DNA 损伤和激活线粒体凋亡途径抑制食管鳞癌细胞增殖
- Author:
Zhongjie WU
1
,
2
;
Yanfei ZHANG
2
;
Wang LV
3
;
Hongxu SHENG
3
;
Linhai ZHU
3
;
Yi HU
2
;
Jian HU
3
Author Information
1. Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, P.R.China;
2. Department of Thoracic Surgery, The First Hospital of Jiaxing, Jiaxing, 314001, Zhejiang, P.R.China
3. Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, P.R.China
- Publication Type:Journal Article
- Keywords:
Esophageal squamous cell carcinoma;
histone methylase G9a;
BIX-01294;
DNA double-strand break;
mitochondrial apoptosis pathway
- From:
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery
2021;28(05):571-577
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects and molecular mechanisms of histone methylase G9a inhibitor BIX-01294 on apoptosis in esophageal squamous cell carcinoma (ESCC). Methods MTT assay and Colony-forming Units were adopted to determine the effects of BIX-01294 on the growth and proliferation of ESCC cell lines EC109 and KYSE150. Flow cytometry was used to analyze the apoptosis status of ESCC cells after the treatment of BIX-01294. The effects of BIX-01294 treatment on the expressions of G9a catalytic product H3K9me2, DNA double-strand break (DSB) markers, and apoptosis-related proteins were detected by Western blotting. Results BIX-01294 inhibited the growth of EC109 and KYSE150 cells in a dose-dependent manner (P<0.05), and BIX-01294 with the inhibitory concentration 50%(IC50) significantly inhibited the formation of colony (P<0.05). After 24 hours treatment of BIX-01294 (IC50), the apoptosis rate of EC109 cells increased from 11.5%±2.1% to 42.5%±5.4%, and KYSE150 cells from 7.5%±0.9% to 49.2%±5.2%(P<0.05). The expression level of the G9a catalytic product, H3K9me2, significantly decreased (P<0.05); while the expression of the DSB marker γH2AX was dramatically enhanced (P<0.05). We also found that the mitochondrial apoptosis pathway was activated and the expression levels of cleaved caspase3 and cleaved PARP were significantly elevated (P<0.05). Conclusion BIX-01294, the inhibitor of methyltransferase G9a, prompted apoptosis in ESCC cells by inducing DSB damage and activating mitochondrial apoptosis pathway.
