The Effect And Mechanism Of Selective COX-2 Inhibitor Combined With EGFR-TKI On Neovascularization Of Transplanted Tumor In Nude Mice With Lung Cancer

Objective:Selective cyclooxygenase-2(C0X-2)inhibitor celecoxib(Celebrex)in combination with epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI)erlotinib(Troquet To study the effects of growth on the growth and proliferation of human lung cancer xenografts in nude mice,and to explore its mechanism at the molecular level.Methods:COX-2 inhibitor combined with EGFR-TKI was used in nude mice xenografts of mutant lung adenocarcinoma HCC827 cells.The growth of tumor-bearing nude mice in each treatment group was observed.The value-added and vascular-related factors were determined by immunohistochemistry.The effect of medication on the growth of lung cancer,the influence of blood vessels and the mechanism.Tumor-bearing nude mice with lung adenocarcinoma mutant HCC827 cells were randomly divided into four groups: control group,celecoxib group(CLX group),tarceva group,celecoxib + tarceva combined group,with1%tween80,celebrex,tarceva,celebrex + tarceva.The above drugs were given to the mice daily and the general conditions(such as mental state,diet and activity level)of each group were observed.Changes in tumor volume were recorded and tumor growth curve was drawn.On the 19 th day,the tumor-bearing nude mice were sacrificed,the tumor body was stripped,the weight and volume of the transplanted tumor were measured,and the tumor inhibition rate was calculated.The transplanted tumor tissue was removed and immunohistochemistry was used to detect the expression of proliferating cell nuclear antigen(PCNA),microvascular density(MVD),vascular endothelial growth factor(VEGF),and platelet growth factor(PDGF),cyclooxygenase(cox-2),epidermal growth factor receptor(EGFR)in each group.Results:1.Growth of tumor-bearing nude mice with lung adenocarcinoma HCC827: tumor inhibition rates of tumor volume in the celecoxib group,the erlotinib group and the combination group were 33.18%,71.61% and 94.20%,respectively.The tumor reinhibition rates of celecoxib group,erlotinib group and the combination group were 34.78%,67.63%and 91.93%,respectively.Compared with the control group,the tumor mass and tumor weight of xenograft in nude mice of all treatment groups showed significant inhibitory effect(P <0.05),while the inhibitory effect was the most obvious in the combined treatment group(P <0.05),indicating that the combined treatment of celecoxib and erlotinib had more significant inhibitory effect on the growth of xenograft in nude mice of lung adenocarcinoma HCC827 than the single treatment group.2.MVD vascular counting test results: the number of MVD in transplanted tumor cells of nude mice with lung adenocarcinoma HCC827 was lower in the single drug group than in the control group(P<0.05),and significantly lower in the combined group than in the single drug group and the control group(P<0.05).The single drug group had an inhibitory effect on tumor angiogenesis,and the inhibitory effect was more obvious after the combination of drugs.3.Immunohistochemical results: PCNA was positively expressed in the transplanted tumor cells of lung adenocarcinoma HCC827 nude mice.The positive expression of PCNA in the monotherapy group was lower than that in the control group,and the difference was statistically significant(P<0.05).VEGF and PDGF showed a brown-yellow diffuse distribution in the cytoplasm of transplanted tumor cells of lung adenocarcinoma HCC827 in nude mice,showing positive expression.The positive expression of VEGF in single drug group was significantly different from that in control group(P<0.05).There was no significant difference between the positive expression of PDGF in CLX group and the control group(P > 0.05).The positive expressions of VEGF and PDGF in the combined group were significantly lower than those in the control group and single drug group,and the difference was statistically significant(P < 0.05).COX-2,EGFR in lung adenocarcinoma HCC827 nude mice transplantation tumor cells in the cytoplasm brown diffuse distribution of positive expression of cox-2 in single medicine group,the positive expression of EGFR is lower than the control group,the difference was statistically significant(P < 0.05),whereas cox-2 in joint group,the positive expression of EGFR was significantly lower than in the control group,positive expression in single medicine group,the difference was statistically significant(P < 0.05).Conclusion:COX-2 inhibitor combined with EGFR-TKI can inhibit the growth and proliferation of lung cancer more than the drug alone by inhibiting tumor angiogenesis and blocking the simultaneous action of the two targets.