| Objective A large number of literature studies have shown that nuclear factor E2 related factor 2(Nrf2),superoxide dismutase(SOD-2)is associated with tumor development.By studying the bioactive Peptide(BAP)derived from goat liver,the regulation of key factors SOD-2 and Nrf2 in the anti-oxidation process of gastric cancer-bearing nude mice was explored,and the role of BAP in inhibiting the development of gastric cancer and its potential application value were explored.Provide scientific basis for in-depth research of BAP.Methods Thirty-five-week-old SPF-class nude mice weighing 12±2 g were selected,male and female,and fed for 3 days.Eight rats were randomly selected as control group(Control Group,CON).CON was not involved in transplanted tumor.Model building.The human gastric cancer cell line BGC-823 with proliferative phase was inoculated into the right flank of nude mice.After pathological confirmation,the tumor was randomly divided into: model group(MG)and low-dose hepatic peptide group(Low Dose of L-BAP).),Middle Dose of M-BAP,High Dose of H-BAP.The intraperitoneal administration was performed according to the doses determined by the previous team: CON(equal volume 0.9% NS),MG group(equal volume 0.9% NS),L-BAP group(0.047 mg/10 g/time),M-BAP group(0.094 mg/10 g/time),H-BAP group(0.188 mg/10 g/time).After continuous administration for 14 days,24 hours after the last administration,the mice were sacrificed by blood in the eyeball and the mice were sacrificed by spine dislocation.The liver tissue and tumor tissue were weighed and the liver index and tumor inhibition rate were calculated.Hepatic and tumor tissues were observed by HE staining.The expression of SOD-2 and Nrf2 in liver and tumor of nude mice was determined by immunohistochemistry.Real-time PCR was used to detect real-time PCR.The mRNA levels of SOD-2 and Nrf2 in the tumor tissues of nude mice were detected.Results(1)Body weight: There was no significant difference in body weight between the groups,and the results were not statistically significant(P ≥ 0.05).(2)Tumor weight: Compared with MG group,the tumor weight of H-BAP group decreased,the difference was statistically significant(P<0.05).(3)Tumor inhibition rate: Compared with MG group,BAP group showed different degrees of tumor inhibition,especially in H-BAP group,the results were statistically significant(P<0.05).In the detached tumor,there was a surface stellate rupture bleeding point in the MG group,and some were accompanied by liquefaction.(4)Liver coefficient: There was no significant difference in liver coefficient between the experimental groups(P ≥ 0.05).From the liver HE staining,no obvious cell necrosis,edema and inflammatory cell infiltration were observed in each group;The HE staining of the tumor showed that the nuclear abnormality and nuclear division of the BAP group were reduced compared with the MG group,especially in the H-BAP group.obvious.(5)Immunohistochemical analysis of changes in SOD-2 and Nrf2 protein expression in the liver: no significant difference in protein expression(P ≥ 0.05).The expression of SOD-2 and Nrf2 protein in the tumor was analyzed by immunohistochemistry.Compared with the MG group,the expression of SOD-2 and Nrf2 protein in the BAP group was decreased,and the difference was statistically significant(P<0.05).(6)Real time-PCR analysis of the expression of SOD-2 and Nrf2 in tumors: Compared with MG group,the relative expression of Nrf2 in nude mice bearing H-BAP and M-BAP groups decreased,the difference was statistically significant.The significance of learning(P<0.05);compared with MG group,the relative expression of SOD-2 in H-BAP and M-BAP group decreased,the difference was statistically significant(P<0.05).Conclusion 1.BAP is expected to be an inhibitor of Nrf2 for clinical use.2.One of the mechanisms by which BAP inhibits the development of gastric cancer: by regulating the oxidative stress pathway,it reverses the excessive oxidative stress and thus inhibits the development of tumor.3.The anti-tumor effect of BAP may act by affecting the expression of the Keap1-Nrf2 pathway-associated gene/protein. |