Sodium Butyrate Induces Apoptosis of Human Colon Cancer Cells by Modulating ERK and Sphingosine Kinase 2  

作　　者：XIAO Min LIU Yun Gang ZOU Meng Chen ZOU Fei 

机构地区：[1]Department of Occupational Health and Occupational Medicine,School of Public Health and Tropical Medicine,Southern Medical University [2]Department of Clinical Laboratory,Affiliated Hospital of Guangdong Medical College [3]Department of Toxicology,School of Public Health and Tropical Medicine,Southern Medical University [4]Department of Endocrinology,Nanfang Hospital

出　　处：《Biomedical and Environmental Sciences》2014年第3期197-203,共7页生物医学与环境科学（英文版）

基　　金：supported by National Natural Science Foundation of China(81272180);National Basic Research Program of China(2012CB518200)

摘　　要：Objective To investigate the role of extracellular signal-regulated kinase （ERK） in apoptosis of human colon cancer （HCT116） cells. Methods After the HCT116 cells were pretreated with specific ERK inhibitor （U0126） or specific siRNA and exposed to 10 mmol/L sodium butyrate （NaBT） for 24 h, their apoptosis was detected by flow cytometry, levels of SphK2 and ERK protein were measured by Western blot, and translocation of SphK2 was assayed by immunofluorescence microscopy. Results The U0126 and siRNAs specific for SphK2 blocked the export of SphK2 from nuclei to cytoplasm and increased the apoptosis of HCT116 cells following NaBT exposure. Over-expression of PKD decreased NaBT-induced apoptosis of HCT116 cells, which was reversed by U0126. Furthermore, transfection of HCT116 cells with constitutively activated PKD plasmids recovered the UO126-blocked export of SphK2. Conclusion ERK regulates the export of SphK2 and apoptosis of HCT116 cells by modulating PKD. Modulation of these molecules may help increase the sensitivity of colon cancer cells to the physiologic anti-colon cancer agent, NaBT.Objective To investigate the role of extracellular signal-regulated kinase （ERK） in apoptosis of human colon cancer （HCT116） cells. Methods After the HCT116 cells were pretreated with specific ERK inhibitor （U0126） or specific siRNA and exposed to 10 mmol/L sodium butyrate （NaBT） for 24 h, their apoptosis was detected by flow cytometry, levels of SphK2 and ERK protein were measured by Western blot, and translocation of SphK2 was assayed by immunofluorescence microscopy. Results The U0126 and siRNAs specific for SphK2 blocked the export of SphK2 from nuclei to cytoplasm and increased the apoptosis of HCT116 cells following NaBT exposure. Over-expression of PKD decreased NaBT-induced apoptosis of HCT116 cells, which was reversed by U0126. Furthermore, transfection of HCT116 cells with constitutively activated PKD plasmids recovered the UO126-blocked export of SphK2. Conclusion ERK regulates the export of SphK2 and apoptosis of HCT116 cells by modulating PKD. Modulation of these molecules may help increase the sensitivity of colon cancer cells to the physiologic anti-colon cancer agent, NaBT.

关 键 词：Sodium butyrate APOPTOSIS ERK Sphingosine kinase 2 Colon caner 

分 类 号：R735.35[医药卫生—肿瘤]