The Study Of The Effect VIP On NKG2D Signal Path And Its Contribution In Immune Escape Of Gastric Cancer

Background:The gastric cancer is the most common malignant tumor of digestive tract. However, carcinomatous change of somatic cell must escape from host immunity killing. The key effect of immune surveillance in natural killer cell is NKG2D signal pathway. The formerly study discovered that the expression of NKG2D in gastric cancer tissues descended, and VIP which taking part in organismic immune suppression increased in some patients with gastric cancer. The signal pathway of between NKG2D and VIP is similar, but their type of action is opposite. Therefore VIP will take part in the immune escape of the gastric cancer through influencing NKG2D signal pathway.Objective:To investigate the influence of VIP to NKG2D signal pathway, and its effect in the immune escape of the gastric cancer.Methods:After NK cells were incubated with VIP, VIP antagonist, NKG2D Ab or correlating signaling molecule inhibitors (PI3K, ERK and NF-κB inhibitor), the expression of proteins and mRNAs of VIP, VPAC1, NKG2D, DAP10, PI3K, ERK and NF-κB in NK cells were detected by immunocytochemistry and RT- PCR. The cytotoxic effect of NK cells to kill MKN45 gastric cancer cells was detected by MTT. Then we analyzed the effect of VIP and each inhibitor on NKG2D signal path, and judged the effect of VIP on NKG2D signal path and its role in the immune escape of the gastric cancer.Results:NK cells had cytotoxic effect on MNK45. VIP and each inhibitor inhibited obviously the cytotoxic effect of NK cells. However, VIP has no effect on each inhibitor. VIP antagonist could reverse the cytotoxic effect of VIP to NK cells, but PAC1 antagonist couldn't.VIP did not excrete by NK cells. VIP or PAC1 antagonist had no effect on the expression of VPAC1 in NK cells. Each inhibitor for PI3K, ERK, NF-κB could inhibit VPAC1 expression.VIP and each inhibitor could inhibit the expressions of NKG2D signal molecules. VIP antagonist could reverse the expression of NKG2D signal molecules, PAC1 antagonist couldn't.Conclusions:The cytotoxic effect of NK cells to MKN45 was related to NKG2D signal pathway. VIP inhibited the cytotoxic effect of NK cell through NKG2D signal pathway, which may be one reason of immune escape of gastric cancer.