The Experimental Study Of The Influence Of WD-3on Inflammatory Microenvironment Of Colorectal Carcinoma And The Clinical Research Of Effect Of Combined With SOX Regimen For Patients With Mid-Advanced Colorectal Cancer

Object:Looking for WD-3targets in each key link in tumor associated macrophages (TAM) through the study of TAM,so as to clarify the role and mechanism of WD-3in colorectal tumor inflammatory microenvironment;To observe the influence of T cell subsets immune environment and tumor markers,the effect of physical condition,clinical symptoms and the side effects of chemotherapy for the patients with ⅢandⅣ stage colorectal cancer after the treatment of WD-3combined with SOX regimen.Methods:By co-culture system,detecting the expression of macrophage M1and M2-type symbolic molecules and TLR2and TLR4receptors;detecting the expression of Th1、 Th2-typecytokines, pro-inflammatory cytokinesIL-8,tumor necrosis factor-a (TNF-a).vascular endothelial growth factor (VEGF),endothelial growth factor (EGF).transformation growth factor-β (TGF-β),matrix metalloproteinase-9(MMP-9) of culture supernatant from different groups; detecting colorectal cancer cell invasion ability and cancer cell protease activity of different groups after co-culture.40cases of Ⅲ/Ⅳ stage colorectal cancer patients are randomly divided into control group (SOX regimen) and treatment group (WD-3+SOX regimen),two groups of patients are observed the chance of T cell subsets immune environment,tumor markers,physical condition.the clinical symptoms and the side effects of chemotherapy after treatment,and statistical analysis the difference between two groups in terms of the above metrics.Results:The research found that compared with the IL-4stimulation group, macrophage subtype of WD-3stimulation group is given priority to with M1type,the expression of TLR2and TLR4receptors on the macrophage of WD-3stimulation group decreased significantly (P<0.01);the expression of IL-2of WD-3stimulation group increased significantly (P<0.01),the expression of IL-4,IL-7of WD-3stimulation group increased (P＜0.05),the expression of IL-6,IL-10of WD-3stimulation group decreased significantly (P<0.01);the expression of IL-8,VEGF, TGF-β of WD-3stimulation group decreased significantly (P＜0.01),the expression of EGF,MMP-9of WD-3stimulation group decreased (P<0.05).The number of CT26in WD-3stimulation group through Transwell membranes significantly lower than the other two groups,the difference is statistically significant (P<0.01);Compared with IL-4stimulation,the protease activity levels of CT26in WD-3stimulation group difference is statistically significant (P＜0.05).And the clinical research find that compared with control group and before treatment,CD3+> CD4+and CD4+/CD8+of the treatment group aecreased significantly (P<0.01);patients in treatment group improve immune function,reduce tumor marker levels,improve physical condition, relieve clinical symptoms and reduce the side effects of chemotherapy,they are better than the control group,the difference was statistically significant (P＜0.05).Conclusion:WD-3can adjust the different subtypes of TAM,inhibit the expression of TLR2and TLR4receptors on the macrophage; recover the balance between Thl type cytokines and Th2type cytokines in tumor inflammatory microenvironment of colorectal cancer;inhibit the expression of IL-8and the generation of TGF-β,reduce the level of VEGF and EGF,inhibit the secretion of MMP-9;reduce the ability of colorectal cancer cell invasion and inhibit the action of the protease activity of colorectal cancer cells.WD-3combined with SOX scheme can improve cellular immune function of patients with Ⅲ and Ⅳ period colorectal cancer,reduce the level of tumor marker,enhance the physical condition (Karnofsky score),ameliorate clinical symptoms and reduce the side effects of chemotherapy.