Intervention Of Aconitine On Treg In Gastric Cancer-bearing Mice By Regulating PGE2/COX2 Pathway

Objective : To study the intervention of aconitine on Treg in gastric cancer-bearing mice by regulating PGE2/COX2 pathway,to explore the possible targets of Chinese herbs to overcome the immunosuppression of tumors,to guide clinical medication,and to provide experimental basis for the development of Chinese herbs targeting Treg cells.Methods :(1)Aconitine was extracted by classical methods such as ultrasound,distillation and dehydration.(2)The inoculated mice were divided into tumor-bearing saline group,aconitine high,medium and low dose group and celecoxib control group.After 24 hours of inoculation,the mice were given intragastric administration.Normal group was not vaccinated and gavaged.(3)After 14 days,eyeball blood was taken,the spleen was sterilized and the tumor tissue(with one side of the skin)was taken,and the inhibition rate was calculated after weighing.The content of PGE2 was detected by ELISA and the proportion of Treg cells in peripheral blood and spleen monocytes was detected by flow cytometry.(4)The remaining inoculated mice were given intragastric administration to observe the overall survival time and general situation.Resuilts:(1)Tumor inhibition rate: Aconitine in high and middle dose groups was55.3%,1.6%,celecoxib group was 30.2%,aconitine in low dose had no anti-tumor effect.(2)Treg ratio in peripheral blood mononuclear cells: There was a significant difference between normal group and normal saline group,and between middle and low dose group of aconitine.Compared with normal saline group,Treg ratio of mononuclear cells in normal group,high and middle dose group of aconitine and celecoxib group was significantly different,and that in low dose group of aconitine was significantly different.There was a significant difference between the high and low dose groups of aconitine.(3)Treg cell proportion of splenic monocytes: Compared with the normal group,Treg ratio of each model group increased significantly,and there was significant difference between the normal saline group and the low dose group of aconitine.There were significant differences between the middle dose group of aconitine and the celecoxib group.Compared with normal saline group,there were significant differences in normal group,high dose group and celecoxib group,and significant differences in middle dose group.Comparisons among aconitine groups:There was a significant difference between high dose and low dose.There were significant differences between middle and low dose groups.Compared with celecoxib group,the low dose group of aconitine had significant difference.(4)Compared with the normal group,the PEG2 content in each model group was significantly higher,and there were significant differences between the normal saline group,the middle and low dose group of aconitine and the celecoxib group.Compared with normal saline group,there were significant differences in normal group,aconitine high,medium dose group and celecoxib group.There were significant differences among the aconitine groups.Compared with celecoxib group,the high and low dose groups of aconitine had significant differences.(5)Compared with normal saline group,the survival time and median survival time of mice bearing gastric cancer in high dose group and celecoxib group were significantly prolonged,the life extension rate was 144.44% and 55.56%,and the effect of high dose group of aconitine was better.There was significant difference between high and low dose groups of aconitine.Conclusion:(1)Aconitine has the most significant anti-tumor effect in high dosage,which is more effective than celecoxib,and low dosage promotes the development of tumors.(2)High dose of aconitine can significantly reduce the proportion of Treg cells in peripheral blood and spleen mononuclear cells of 615 mice bearing gastric cancer,which is more effective than celecoxib.High dose of aconitine can delay the progression of cancer and reverse the immune escape of cancer,and low dose can promote the expression of Treg.(3)High dose aconitine can mediate PGE2/COX2 pathway to regulate Treg immunosuppression in gastric cancer bearing mice and play an anti-tumor role.(4)The anti-tumor immunosuppressive effect of aconitine is dose-dependent and bidirectional.And the anti-tumor effect is better than celecoxib.(5)Aconitine at high dosage significantly prolonged the survival and median survival of 615 mice bearing gastric cancer,which was more effective than celecoxib.Aconitine at low dosage promoted the development of tumors.