丙戊酸钠通过EGFR下调CD44表达抑制胶质瘤细胞生长

目的:探讨丙戊酸钠通过抑制A172胶质瘤细胞表皮生长因子受体（epidermal growth factor receptor，EGFR）的活化，下调CD44表达，进而调节细胞生长的机制。方法:实时荧光定量PCR和Western blot检测A172胶质瘤细胞中CD44以及siRNA下调CD44表达的情况，MTT检测CD44和丙戊酸钠对细胞生长的影响，Western blot检测丙戊酸钠对细胞中p-EGFR、EGFR和CD44表达影响。结果:丙戊酸钠抑制A172胶质瘤细胞生长，并具有浓度依赖性。A172胶质瘤细胞表达CD44，siRNA下调CD44表达后，细胞生长较正常组显著减缓。活化EGFR促进A172胶质瘤CD44蛋白表达，而EGFR的抑制剂Lapatinib可显著抑制上述效应。丙戊酸钠抑制EGFR磷酸化，下调CD44蛋白表达。结论:丙戊酸钠抑制A172胶质瘤细胞的生长。抑制A172胶质瘤细胞中EGFR的活化，下调CD44的表达，是丙戊酸钠抑制胶质瘤细胞生长的其中一个机制。

Sodium valproate inhibits the growth of glioma cells by down-regulation of CD44 expression through EGFR

Objective:To investigate the mechanism that sodium valproate regulating the growth of cell by inhibiting the activation of epidermal growth factor receptor (EGFR) and down-regulating the expression of CD44 in A172 glioma cells.Methods:Real-time fluorescence quantitative PCR and Western blot were used to detect the expression of CD44 in normal and siRNA-treated A172 glioma cells.MTT was used to detect the effects of CD44 and sodium valproate on A172 glioma cell growth.Western blot was used to detect the effects of EGF and sodium valproate on the expression of p-EGFR，EGFR and CD44 in A172 glioma cells.Results:The growth of A172 glioma cells were inhibited by sodium valproate in a concentration-dependent manner.CD44 was expressed in A172 glioma cells and there was significant decrease in the cell growth compared in the normal group when CD44 was down-regulated by siRNA.Activation of EGFR promoted the expression of CD44 protein in A172 glioma cells，while the above effect was significantly inhibited by Lapatinib，a EGFR inhibitor，in A172 glioma cells.Sodium valproated inhibited EGFR phosphorylation and down-regulated the expression of CD44 protein in A172 glioma cells.Conclusion:Sodium valproate inhibited the growth of A172 glioma cells.Inhibition of the activation of EGFR and down-regulation of the expression of CD44 are one of the mechanisms of sodium valproate to inhibit the growth of glioma cells.