Evaluation of anti-angiogenic effects of 5HT2A rec antagonist in xenograft model of colon cancer and expression of VEGF,NfKB,BAX,Caspase9 and Bcl2

Abstract

Abstract Background . One of the most common cancers of the gastrointestinal tract is colorectal cancer, according to some studies, serotonin can play a proliferative role by stimulating the cAMP-dependent MAPK pathwayAlso there are some evidences about role of 5HT receptors in some cancers as gastrointestinal,breast and bladder and breast cancers . Objective According to these backgrounds,we have aimed to investigate the effect of 5HT2A receptor antagonist (ritanserin) on expression of apoptotic and angiogenesis factors as (VEGF,NfKB) and Bax and Bcl2 in an In vivo model in nude mice . Methods The drugs were injected into mice for 21 days, and intradermal tumor was induced by injecting 10,000,000(HT29) suspension of colorectal cell into the flank muscle of nude mice. Tumor size were examined macroscopically three times a week. After three weeks, the mice were killed and the tumor tissue was removed and the Real-time PCR method was used to evaluate the angiogenic genes of VEGF and NfKB and Bax,Caspas9 and Bcl2 protein expression. The DATA analyzed by Friedman test and One-way ANOVA and post TUKEY-TEST with 21 SPSS software with P value < 0.05 Results In There was a significant difference in the expression of bcl2 gene in the drug groups compared to the control group P < 0.05.The expression of bcl2 gene in drug groups has decreased compared to the control group,P < 0.05.The results of Kruskal-Wallis test in the expression of caspase9 gene showed inequality in the mean expression of caspase9 gene in the groups. The effect of ritanserin on the expression of angiogenesis factors in cells isolated from nude mice by RT-PCR showed that the level of the expression of nfkb in ritanserin group (4/73) and cis group (0/17) was lower than rit-cis groups(13/88) and control(1/00)The expression level of VEGF factor in rit group (3.26) was lower than cis group (4.90) which indicates the inhibitory effect of ritanserin is evenly more than positive control(cisplatin)on the expression of angiogenesis genes. Conclusion Our study has shown that Ritanserin as 5HT2A receptor antagonist has anti-tumor and anti-angiogenic effect in xenograft model in nude mice which some parts of its' effect could be through inhibition of NfKB as an inflammatory factor and VEGF as angiogenic factor and also through affecting on apoptotic factors as Bax,Bcl2 and Caspase9.