[Chidamide inhibits proliferation and promotes apoptosis of esophageal squamous cell carcinoma cells by inhibiting the PI3K/Akt and ERK1/2 pathways and increasing DNA damage].

objectiveTo investigate the mechanism mediating the inhibitory effect of chidamide on esophageal squamous cell carcinoma (ESCC) cells.

methodsESCC cell lines KYSE-150, KYSE-450 and KYSE-510 were treated with 5, 10, 20, or 40 μmol/L of chidamide, and the changes in cell proliferation, colony-forming capacity, cell apoptosis and cell cycle were assessed using MTT aasay, colony formation experiment and flow cytometry. Western blotting was performed to detect the expression levels of cleaved caspase-3, cleaved PARP, p21, cyclin D1, p-Akt, p-ERK1/2, γH2AX, H3K9ac, and Ki-67. In a nude mouse model bearing subcutaneous ESCC xenografts, the effects of intraperitoneal injection of 20 mg/kg chidamide for 3 days on tumor size and body weight were observed every 3 days, and Ki-67 and CD31 expressions in the tumor tissues were detected using immunohistochemistry. Tubular formation experiment was used to examine the effect of chidamide on tubular formation of human umbilical vein endothelial cells (HUVECs)

resultsIn cultured ESCC cell lines, chidamide significantly inhibited cell proliferation and colony formation (

conclusionChidamide inhibits proliferation, induces apoptosis and blocks cell cycle of ESCC cells possibly by inhibiting the PI3K/Akt and ERK1/2 pathways and increasing DNA damage. Chidamide also inhibits subcutaneous tumorigenesis of ESCC cells in mice by inhibiting tumor cell proliferation and angiogenesis.