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Outline
To explore the effects of histone deacetylase inhibitor chidamide on the proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of murine triple-negative breast cancer 4T-1 cells.
CCK-8 method was performed to analyze the effects of chidamide on the proliferation of 4T-1 cells; flow cytometry to detect the effects of chidamide on the cell cycle and apoptosis of 4T-1 cells; Western Blot to detect intracellular histone deacetylase 5, lysine-specifc demethylase 1 and EMT-related proteins E-cadherin, Vimentin, MMP-9, MMP-2 expression; Transwell method to analyze the effect of chidamide on the migration and invasion of 4T-1 cells; HE staining method to observe the pulmonary metastasis of tumor tissues and the toxicity of chidamide on mice; ELISA method to analyze the effect of chidamide on the immune system in mice.
The results of CCK-8 method showed that chidaniline had the ability to prominently inhibit the proliferation of 4T-1 cells, and its 24 h IC50 value was 43.42 μmol·L-1. Chidamide could induce G2/M phase arrest and apoptosis of 4T-1 cells. At the same time, it was found that chidamide distinctly down-regulated the mRNA and protein expression of HDAC5 in 4T-1 cells, but only down-regulated the protein expression of LSD1; in addition, the expressions of EMT-related factors E-cadherin, vimentin, MMP-9, MMP-2 were notably down-regulated. Transwell experiments found that chidamide obviously inhibited the migration and invasion of 4T-1 cells. In vivo, chidamide of 10 mg·kg-1 showed an outstanding suppression effect on the proliferation and pulmonary metastasis of 4T-1 cells in tumor-bearing mice, but did not affect the body weight and the morphology of heart, liver, and kidney tissues.
Chidamide can depress the expression of HDAC5, LSD1 and EMT-related proteins E-cadherin, Vimentin, MMP-9, MMP-2, and inhibit the proliferation and migration of 4T-1 cells both in vivo and in vitro, indicating that chidamide has a great potential for clinical anti-triple-negative breast cancer treatment.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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