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 U0126-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.

It has been demonstrated that patients with asthma have a large number of NK cells and show a stronger NK activity. These results indicate that NK cell activity may be related to total IgE level in serum in healthy subjects. Previously,we have found that sodium butyrate (NaBu) markedly enhanced the IL-4-induced IgE production in the LPS-stimulated murine splenocytes in vitro, and inductive rat IgE production in vivo, and enhanced the NK cell activity ex vivo .We hypothesized that the IgE production might be involved in butyrate-enhanced NK cell activity in vivo. Mice were intraperitoneally treated/immunized with NaBu or/and Ascaris suum extract (ASC),and the spleen NK cell activity was evaluated. Furthermore, the effect of serum (NAS) on IL-2-or IFN-γ -induced spleen NK cell activity was determined. The spleen NK cell activity and IL-2-or IFN-γ -induced spleen NK cell activity of mice treated/immunized with NaBu or/and ASC were stronger than those of untreated/unimmunized mice. Although IL-4 blocked IL-2 (100 U/ml)-or IFN-γ (100 U/ml)-induced increase in NK cell activity,these NK cell activities in mice treated/immunized with NaBu/ASC were not inhibited. IgE production showed a tendency to rise in NaBu-treated mice serum, and a synergistic effect was observed with treatment of NaBu and ASC. Moreover, the NAS significantly increased IL-2(25 U/ml)-or IFN-γ (25 U/ml)-induced NK cell activity, and its effect was inhibited by anti-mouse IgE mAb.