Study On The Effect And Mechanisms Of Lycopene Intervention On The Occurence And Progression Of Esophageal Cancer Based On PPAR?

ObjectiveTo observe the effects of lycopene on body weight,carcinogenesis of esophageal mucosa,serum levels of oxidative stress factors and expression of related proteins in esophageal tissues of rats with esophageal cancer,and to explore the intervention effect and possible mechanisms of esophageal cancer in rats.MethodsA total of 75 male F344 rats at five to seven weeks of age were randomly divided into five groups according to their body weight:Group A was solvent control group,group B was carcinogenic group,group C was low-dose lycopene intervention group(10 mg/kg body BW),group D was medium-dose lycopene intervention group(25 mg/kg BW),and group E was high-dose lycopene intervention group(50 mg/kg BW).Rats in group A and B were fed with normal diet,while rats in group C-E were fed with diets containing low,medium and high doses of lycopene respectively.The intervention was completed after 25 weeks.Rats in each group were subcutaneously injected(0.1mL/100g BW),rats in group A were subcutaneously injected with 20%Dimethyl solfoxide(DMSO),and rats in group BE were subcutaneously injected with NMBzA with 20%DMSO as solution(0.35mg/kg BW),three times a week for five weeks.Intervention at the end of 25 weeks:HE staining results of esophageal mucosa tissue of rats were observed by microscope;serum levels of malondialdehvde(MDA),glutathione peroxidase(GSH-PX)and superoxide dismutase(SOD)were measured by corresponding kits and the expression levels of peroxisome proliferator-activated receptor ?(PPARy),nuclear transcription factor Kappa B(NF-?B),cysteinyl aspartate specific proteinase-3(Caspase-3)and cyclooxygenase-2(COX-2)proteins in esophageal mucosa was detected by Western blot.SPSS 21.0 software was used for statistical analysis,and a=0.05 was used as the test level.Results1.The incidence of esophageal neoplasms and HE staining results showed that:The incidence of esophageal neoplasms in each group was different,and the difference was statistically significant(?2=24.49,P<0.05).No tumors were found in the esophagus of group A and in group B-E,tumors were found in the esophagus of rats.The incidence of tumors was 73.33%,20.00%,13.33%and 13.33%respectively.The incidence of esophageal tumors in group C,D and E was lower than that in group B,with statistical significance(P<0.05).However,there was no significant difference in the incidence of tumors among group C,group D and group E(P>0.05).Distribution of pathological types of esophageal mucosa in rats of each group was different(H=45.47,P<0.05).In group A,only normal epithelium(60.0%)and simple hyperplasia(40.0%)were found,while in group B,esophageal tumors(73.3%)were found.Abnormal hyperplasia was common in group C,D and E(73.3%,60%and 73.3%,respectively).There were significant differences in the distribution of pathological types of esophageal mucosa between group A and the other four groups(all P<0.05).The distribution of pathological types of esophageal mucosa in group B was significantly different from that in group D(P<0.05).2.The results of oxidative stress factors in rat serum showed that:The activity of GSH-PX in group C,group D and group E was higher than that in group B(all P<0.05).There were significant differences in serum GSH-PX activity between group D and group C and group E(all P<0.05).The activity of SOD in serum of group D and group E was higher than that of group B,the difference was statistically significant(P<0.05),but there was no significant difference between group D and group E(P>0.05).The serum MDA levels in group D and group E were lower than those in group B,and the difference was statistically significant(P<0.05).3.Western blot results showed that the expression level of PPARy in esophageal mucosa of rats:Compared with group A,the expression level of PPARy in esophageal mucosa of group B was lower,with significant difference(P<0.05).Compared with group B,the expression level of PPARy protein in group D and group E increased significantly(P<0.05),while there was no significant difference between group C and group B(P>0.05).In the three groups of lycopene intervention group(C,group D,group E),compared with group C,the expression level of PPARy protein in esophageal mucosa of group D and group E increased,and the difference was statistically significant(P<0.05).Compared with the other groups(group B,group C,group D,group E),the expression of PPARy protein in esophageal mucosa of group D rats increased,and the difference was statistically significant(P<0.05).The expression level of NF-?B protein in esophageal mucosa of rats:Compared with group A,the expression level of NF-?B in esophageal mucosa of rats in group B,C and E increased significantly(all P<0.05),while there was no significant difference between group D and group A(P>0.05).Compared with group B,the expression level of NF-?B protein in group C,D and E decreased significantly(P<0.05).Compared with group C,the expression of NF-?B protein in group D and group E decreased,and the difference was statistically significant(P<0.05).COX-2 protein expression level in esophageal mucosa of rats:Compared with group A,COX-2 protein expression level in group B increased significantly(p<0.05).Compared with group B,the expression of COX-2 protein in group C,group D and group E decreased,and the difference was statistically significant(P<0.05).Compared with group C,COX-2 levels in esophageal mucosa in group D and E decreased significantly(P<0.05).Compared with other groups(group B,group C,group D,group E),the expression of COX-2 protein in esophageal mucosa of group D rats decreased,and the difference was statistically significant(P<0.05).The expression level of Caspase-3 protein in esophageal mucosa of rats:Compared with group B,the expression level of Caspase-3 protein in group C,group D and group E increased,and the difference was statistically significant(P<0.05).Compared with C group,the expression of Caspase-3 protein in esophageal mucosa of group D and E increased significantly(P<0.05).Compared with other groups(group B,group C,group D,group E),the expression of Caspase-3 protein in esophageal mucosa tissue of group D rats increased,and the difference was statistically significant(P<0.05).Conclusions1.Appropriate does of lycopene intervention can inhibit the carcinogenesis and development of esophageal mucosa in rats.2.Appropriate does of lycopene intervention can increase the level of GSH-PX,SOD and decrease the level of MDA in serum of esophageal cancer rats.3.Appropriate does of lycopene intervention can up-regulate the expression of PPAR? and Caspase-3 protein and down-regulate the expression of NF-?B and COX-2 protein in esophageal cancer tissues of rats.