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
3
;
Wang LV
4
;
Hongxu SHENG
4
;
Linhai ZHU
4
;
Yi HU
3
;
Jian HU
4
Author Information
1. 1. Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, P.R.China
2. 2. Department of Thoracic Surgery, The First Hospital of Jiaxing, Jiaxing, 314001, Zhejiang, P.R.China
3. Department of Thoracic Surgery, The First Hospital of Jiaxing, Jiaxing, 314001, Zhejiang, P.R.China
4. 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.
