Evaluation of growth and angiogenesis inhibition effect of Ritanserin on COX2 and EGFR in model of HT29 (colon cancer) incubation in nude mice

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 (Cox2 and EGFR) 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 EGFR and COX2 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 control group, there was no significant difference between tumor volumes on the three dates.( p-value = .166( and In Ritanserine-Cisplatin group, there was significant difference between tumor volumes on the three dates(p-value = 0.018)..And the difference between the first and third times.( p-value = 0.014.Also in Ritansern group, There is a significant difference between the first and third times,( p-value = 0.009). But there is no significant difference between the second and third times (p-value = 0.024).,The effect of ritanserin on the expression of inflammatory(Cox2) and angiogenesis(EGFR) factors in tumors have shown that expression of cox2 gene in cisplatin group has been increased (51/63 compared with control .Also ritanserin have increased this expression (11/31) compared with control(1/00) and this effect for cis-rit was more pronounced (70/71)and this effect for both ritanserin and rit-Cis was not significant compared with control.P > 0.05 .Also expression of EGFR as an angiogenic factor was increased by ritanserine (6.23) and combination of rit + cis had synergistic effect (36.28) 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 COX2 as an inflammatory factor and EGFR as angiogenic factor .