丁酸钠对前列腺癌LNCaP细胞HER-2信号通路的影响
Targeting HER-2 Signal Pathway in LNCaP Prostate Cancer Cells by Sodium Butyrate
-
摘要: 目的 研究组蛋白去乙酰化酶抑制剂丁酸钠对前列腺癌LNCaP细胞HER-2信号通路的影响，探讨其抗肿瘤作用的分子机制。方法 四甲基偶氮唑蓝(MTT)检测药物对肿瘤细胞增殖的影响；hoechst 33342染色观察细胞凋亡的形态学变化，Western blot检测凋亡标志蛋白、HER2/ neu、Phos-Akt、Phos-Erk等信号蛋白的表达。结果 丁酸钠能够有效抑制LNCaP细胞的增殖并诱导细胞凋亡，半效杀伤剂量（EC50）为5.6mmol/L；药物能够抑制HER-2基因的转录和蛋白的表达，并抑制下游信号通路中MAPK和AKT的活化。结论 丁酸钠能够阻断对前列腺癌细胞生长具有重要作用的HER-2信号通路，从而对肿瘤细胞发挥抑制作用。Abstract: Objective To investigate the mechanisms underlying the antitumor effect of histone deacetylase inhibitor sodium butyrate on LNCaP prostate cancer cells. Methods Proliferation of LNCaP cells exposed to sodium butyrate was detected by MTT assay. Cell apoptosis was assayed by hoechst 33342 nuclei staining as well as apoptosis marker protein leaved PARP expression. The expression of HER-2 as well as downstream key signaling molecules was assayed by western blotting after sodium butyrate exposure. Results Sodium butyrate killed LNCaP cells with an EC50 value of 5.6mmol/L within 48 hours as well as inducing cell apoptosis. Sodium butyrate could downregulate HER-2 expression through suppression of HER-2 gene transcription.Activation of downstream signaling molecules such as Akt and Erk were also suppressed. Conclusion Sodium butyrate exhibits significant antitumor effect against LNCaP cells through suppression of HER-2 signaling pathway.
下载:
