Study Of Xiaotan Sanjie Decoction In Inhibiting Lymphatic Metastasis By Regulating VEGF Signaling Pathway In Gastric Cancer

ObjectiveBy collecting different gastric disease and gastric cancer clinical samples,as well as the samples after the intervention of Xiaotan Sanjie decoction,observeing the density of micro-lymphatic vessels by the marker of LYVE-1 and the expression of VEGF cell signaling pathway: 1.Analyze the expression of VEGF-C/D,VEGFR-3 in chronic superficial gastritis,gastric polyps,specialized intestinal metaplasia and cancer central as well as its invasive edge.2.Seclect partial patients randomly,observe the variation of micro-lymphatic vessels and the expression of VEGF-C/D,VEGFR-3 before and after the treatment of Xiaotan Sanjie decoction.3.Estimate the correlation of the micro-lymphatic vessels and the expression of VEGF-C/D,VEGFR-3 and other clinical parameters.MethodsAfter the complete of the Informed Consent and Ethical Review Approvement,we further formulated detailed exclusion and inclusion criteria and then collected different clinical specimens from the patients.1.The patients were divided into the following groups: Control group(chronic superficial gastritis),Gastric cancer before the disease group(gastric polyps),Precancerous lesion group(specialized intestinal metaplasia),n=20 respectively.And different location of gastric cancer group(central and invasive edge),n=20.We further selected 20 patients from the cancer group and delived Xiaotan Sanjie decoction treatment for continuous 6 months,and then obtained the samples by biopsy.2.We chose the lymphatic vessel endothelial hyaluronan receptor-1(LYVE-1)as marker to observe the new borned micro-lymphatic vessels by the immunohistochemical staining.Real-time PCR and Western Blot was used to dectced the protein and mRNA expression of VEGF-C/D?VEGFR-3.3.By the statistical method includes Student-t test,ANOVA anlysis,Chi-Squaret test and etc.,to test the correlation of new borned micro-lymphatic vessels with the expression of VEGF-C/D?VEGFR-3;check variation of the new borned micro-lymphatic vessels and the expression of VEGF-C/D?VEGFR-3 before and after the treatment of Xiaotan Sanjie decoction;analyze the new borned micro-lymphatic vessels with the clinical parameters for the patients.Results1.The expression of the new borned micro-lymphatic vessels was different in different gastric disease,among these,no obvious new borned micro-lymphatic vessels was detected in the Control group(chronic superficial gastritis),Gastric cancer before the disease group(gastric polyps)and some were detected in Precancerous lesion group(specialized intestinal metaplasia),however,no significant statistical differences were detected inside these groups(P>0.05).In the gastric cancer group,obvious new borned micro-lymphatic vessels were found no matter in the central or in the invasive edge of the tumor.In particular,we found more new borned micro-lymphatic vessels with intact structures;it displayed significant statistical differences when compared with the central of the tumor(P<0.05).2.The expression of the mRNA and protein of VEGF-C/D,VEGFR-3 was positively correlated with the new borned micro-lymphatic vessels,however,its expression was low in the Control group,Gastric cancer before the disease group and Precancerous lesion group,no significant statistical differences were found among these groups(P>0.05).The VEGF-C/D?VEGFR-3 were highly expressed in the cacner tissues,it shows significant statistical difference when compared with the aforementioned groups(P<0.05),of note,the mRNA and protein of VEGF-C/D were significant different in the central when compared with the invasive(P<0.05)edge of the tumor,however,no such differences were detected in VEGFR-3(P>0.05).3.The treatment of Xiaotan Sanjie decoction could have a role in decrease the expression of the new borned micro-lymphatic vessels and the expresiion of VEGF-C could correspondingly down-regulated,significant statistical differences could be found before and after the administration(P<0.05).However,no such differences could be found concering the mRNA and protein expression of VEGF-D and VEGFR-3(P>0.05).4.The density new borned micro-lymphatic vessels of gastric cancer was found to be correlated with the T,N,M stage,the diffretiation of the cells as well as the lymphatic metastasis.Except these,the VEGF-C/D also represents an apparent correlation with it,however,no such correlation could be observed in VEGFR-3.5.The treatment of Xiaotan Sanjie decoction could decrease the new borned micro-lymphatic vessels,and in particular,VEGF-C was more consistent with the vessles,VEGF-D and VEGFR-3 shows no such coincidence.Conclusion1.The new borned micro-lymphatic vessels was expressed differently in different gastric diseases,compared with other non-malignant disorders,the new borned micro-lymphatic vessels was extremely high in the cancer tissues.More attractively,the expression of these vessles was nore obvious in the invasive edge than in the central of the tumor,which may hint that these vessles could potentially associate with the lymphatic metastasis.2.The expression of VEGF-C/D and VEGFR-3 could play an important role in the regulation of the new borned micro-lymphatic vessels.Among them,VEGF-C/D is of particularly important,which may suggest that these points would be served as therapeutic targets in future.3.The Xiaotan Sanjie decoction could decrease of the new borned micro-lymphatic vessels,and its potential mechanism would be laid on decrease the expression of VEGF-C.