Selective COX-2 Inhibitor Combined With EGRF-tyrosine Kinase Inhibitor Study On The Proliferation?Immunization Of Lung Cancer Cells And Its Mechanisms

Objective The selective cox-2 inhibitor celecoxib(CLX)joint EGFR-TKI it for his role in lung adenocarcinoma cancer cell strains(HCC827)a tumor-burdened nude mice model,the subsequent testing within the tumor cells proliferation related factors: proliferating cell nucleus antigen(PCNA),ring oxidase-2(COX-2)and epidermal growth factor receptor(EGFR),immune regulating factor: transforming growth factor beta(TGF-?),serum interleukin 6(IL-6),serum interleukin 8(IL-8),explore the drug combination for lung cancer cell proliferation,immune effects and mechanisms.Methods(1)A total of 24 Outsourcing qualified(HCC827)tumor-bearing nude mouse models were randomly divided into 4 groups: control group,celexib group(CLX group),erlotinib group,and celexib + erlotinib group(combined group),Control group: 1%tween80solution was perfused through the stomach.CLX group: the same amount of CLX solution was injected through the stomach.Erlotinib group: equal amount of erlotinib solution was injected through the stomach.Combined group: gastric infusion of CLX solution and erlotinib solution continued for 17 days.(2)During the administration period,the general conditions of the nude mice in each group,such as food intake,activity,color and reactivity and other indicators,were closely observed.The tumor diameter of the nude mice with tumor was measured every 1 day.On the 17 th day,the nude mice with tumor were put to death.(3)The expression levels of PCNA,COX-2 and EGFR proteins in tumor-bearing nude mice were measured by immunohistochemistry.(4).ELISA was used to measure the expression levels of the immune factors IL-6 and IL-8 in the serum of the transplanted lung adenocarcinoma HCC827 nude mice,and the expression levels of the immune factor TGF-? in the cells were measured by immunohistochemistry.(5)Statistical methods:SPSS 25.0 software was used forstatistical analysis.The measurement data were expressed by means of mean ± standard deviation(x ± s).T-test was used for the comparison of the mean of the two groups of samples.Single factor analysis of variance was used for the comparison of the mean of the multiple groups of samples,and the difference was statistically significant(P < 0.05)?Results(1)According to the measurement results and calculation,the tumor inhibition rates of CLX group,erlotinib group and combined group were 33.18%,71.61% and 94.20%,respectively,and the tumor inhibition rates were 34.78%,67.63% and 91.93%,respectively.The results showed that the tumor-inhibiting rates of CLX group,erlotinib group and combined group were all greater than those of the control group,with statistically significant differences(P <0.05).In addition,the tumor-inhibiting rates of the two monotherapy groups were significantly lower than those of the combined group,with statistically significant differences(P < 0.05).(2)Immune-related expression results(ELISA+ immunohistochemistry): serum IL-6 and IL-8expression levels in CLX group were lower than those in the control group,and the difference was statistically significant(P<0.05).The expression levels of serum IL-6 and IL-8 in CLX+erlotinib group were lower than those in the control group,CLX group and erlotinib group,and the difference was statistically significant(P<0.05).The immunogenic factor TGF-? was positively expressed in cytoplasm.Positive expression of TGF-? in CLX+erlotinib group was significantly lower than that in the control group,CLX group and erlotinib group,with statistically significant differences(P < 0.05).(3)Results of proliferation-related expression(immunohistochemistry): PCNA in HCC827 lung cancer cells was brown-yellow positive expression(in the nucleus),COX-2 was brown-yellow positive expression(in the cytoplasm),and EGFR was brown-yellow positive expression(in the nucleus and cytoplasm).The positive expression intensity of PCNA and COX-2 in the control group was higher than that in the CLX group,and the difference was statistically significant(P<0.05).The positive expressions of PCNA,COX-2 and EGFR in the combined group were significantly lower than the other three groups,and the difference wasstatistically significant(P < 0.05).Conclusion(1)This animal experiment showed that CLX combined with erlotinib could weaken the expression of cell proliferation factors PCNA,COX-2 and EGFR,and inhibit the growth and proliferation of lung tumor cells.(2)CLX combined with erlotinib can down regulate the expression of IL-6,IL-8,TGF-?,play the immunomodulatory function and may also participate in the anti-tumor effect.(3)Selective cox-2 inhibitors combined with EGFR-TKI can significantly enhance the anti-tumor effect of lung cancer,which may become a kind of adjuvant anti-tumor drugs.