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Selective COX-2 Inhibitor Celecoxib Combined With Erlotinib Study On The Growth Of Lung Cancer And Its Mechanisms

Posted on:2020-05-25Degree:MasterType:Thesis
Country:ChinaCandidate:W P SunFull Text:PDF
GTID:2404330590487603Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective To investigate the effects of selective COX-2 inhibitor celecoxib(CLX)combined with erlotinib(Troquet)on the growth and proliferation of lung cancer in vivo,and to detect proliferating cell nuclear antigen(PCNA)and loop by detecting proliferation-related factors.Oxidase-2(COX-2),epidermal growth factor receptor(EGFR),apoptosis-related factor p53 tumor suppressor gene(p53),B-cell lymphoma-2 gene(BCLl-2)explore its mechanism at the molecular level.Methods 1.Purchased EGFR gene mutant lung adenocarcinoma cell line(HCC827)tumor-bearing nude mice were randomly divided into 4 groups and used: control group:gastric perfusion 1% tween80 solution;celecoxib group(CLX group): stomach Perfusion of CLX solution;erlotinib group(Troquet group): gastric perfusion Tarceva solution;celecoxib+ erlotinib group(CLX + Tarceva group): gastric perfusion CLX solution and Tarceva solution For 17 days;the tumor diameter of the tumor-bearing nude mice was measured every other day during the administration,and the tumor growth curve was drawn to observe the changes of the mental,diet and body weight of the nude mice.2.Calculate the tumor inhibition rate: On the 17 th day,the tumor-bearing nude mice were sacrificed,the tumor tumor was removed,the tumor diameter and weight were measured,and the tumor weight and volume inhibition rate were calculated.3.The apoptotic index of lung adenocarcinoma cells in each group of transplanted tumor tissues was detected by in situ end-labeling(tunel)fluorescence method.4.Immunohistochemical method was used to detect the expression of cell proliferation factors PCNA,COX-2,EGFR,apoptotic factors P53 and BCL-2 in nude mice xenografts of HCC827 nude mice,and to explore the relationship between CLX and TCL.The mechanism of Kai's influence on the growth and apoptosis of lung cancer.Results The results of combination of celecoxib and Tarceva on tumor growth and apoptosis showed that: 1.The tumor volume inhibition rate of the three groups of CLX group,Tarceva group and CLX+ Tarceva group was 33.18.%,71.61% and 94.20%,the tumor weight inhibition rate was 34.78%,67.63% and 91.93%,respectively.The tumor inhibition rate of CLX+ Tarceva group was significantly higher than that of the control group and the two single drug groups(CLX group,Tarceva group),and the difference was statistically significant(P<0.05).The results of tunel test showed that the apoptotic index of CLX group was significantly higher than that of the control group(P<0.05).The apoptosis index of CLX+Tarceva group was higher than that of the control group,CLX group and Tarceva group.The difference was statistically significant(P<0.05).3.Immunohistochemical results: In the control group HCC827 cells,PCNA was brown-yellow in the nucleus,COX-2 was brown-yellow in the cytoplasm,and EGFR,P53 and BCL-2 were in the nucleus and cells.The pulp was positively expressed in brownish yellow.The positive expressions of PCNA,COX-2,P53 and BCL-2 in the CLX group were lower than those in the control group,and the difference was statistically significant(P<0.05).The positive expressions of PCNA,COX-2and EGFR in CLX+ Tarceva group were significantly lower than those in the control group,CLX group and Tarceva group,and the difference was statistically significant(P<0.05).The positive expressions of P53 and BCL-2 in the CLX+ Tarceva group were significantly lower than those in the control group,CLX group and Tarceva group,and the difference was statistically significant(P<0.05).Conclusion 1.The selective COX-2 inhibitor CLX alone can inhibit the growth and proliferation of lung adenocarcinoma and induce apoptosis.When combined with Tarceva,the effect is more obvious.2.Selective COX-2 inhibitor CLX combined with Tarceva inhibits the growth and proliferation of lung adenocarcinoma and induces apoptosis.It may down-regulate the expression of cell proliferation factors such as PCNA,COX-2 and EGFR,and down-regulate apoptotic factors.BCL-2,P53 and other expressions are related.3.Selective COX-2 inhibitor CLX combined with Tarceva may become a new method for the treatment of lung cancer.
Keywords/Search Tags:celecoxib, erlotinib, cell proliferation, apoptosis, HCC827 cells
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