The Angiotensin Ⅱ Promotes Tumor Proliferation And EMT Via TGF-β/Smad Signaling Pathway In Colon Cancer

Objective:Angiotensin Ⅱ type 1 receptor(AT1R)is involved in the occurrence and development of multiple human cancers.However,the role of AT1 R in colon cancer is unclear.The purpose of this study is to investigate the expression of AT1 R in colon cancer cells.the effects of Angiotensin Ⅱ and losartan on cell proliferation,migration,invasion and EMT in colon cancer cells,and further detect its molecular mechanism in vitro.At last investigate the effect of losartan on colon cancer growth in vivo.This research might provide a new therapeutic target for the treatment of colon cancer patients.Methods:We analysed the relationship between AT1 R expression and 5-year survival rate in colon cancer patients in the bioinformatics database.The expression of AT1 R in CT26 colon cancer cells was detected by immunofluorescence and Western blot.CCK-8 assay,plate colony assay,migration and invasion assay were employed to detect the abilities of Angiotensin Ⅱ and losartan on the proliferation,migration and invasion in colon cancer cells.Western blot was used to detect the invasion-related protein,MMP2 and MMP9.Western blot was employed to detecte the expression of E-cadherin,N-cadherin,α-SMA and Snail.Furthermore,we taken Western blot to detect the expression of TGF-β/Smad pathway related proteins.The effect of losartan on the growth of colon cancer was detected in vivo.Results:Firstly,we find that compared with high expression AT1 R colon cancer patients,the 5-year survival rate is higher in those patients with low expression of AT1 R.The AT1 R is expressed on CT26 cell membrane,angiotensin Ⅱ can up-regulate the expression of AT1 R.Angiotensin Ⅱ enhances the proliferation,migration and invasion ability(P < 0.05)and increases the expression of MMP2 and MMP9.Ang Ⅱ also down-regulates the expression of E-cadherin,and up-regulates mesenchymal-related markers including N-cadherin,α-SMA and Snail.We find that losartan can antagonize the effects induced by angiotensin Ⅱ(P < 0.05).We identify that Ang Ⅱ up-regulates TGF-β,p-Smad2 expression(P<0.05).Conversely,losartan produces the opposite effect.Additionally,in vivo,losartan significantly inhibited the growth of colon cancer(P<0.05).Conclusion:Compared with high expression of AT1 R colon cancer patients,the low expression of AT1 R colon cancer patients get a higher 5-year survival rate.angiotensin Ⅱ promotes the ability of proliferation,migration and invasion in colon cancer cells.Accordingly,it is suggested that Ang Ⅱ promotes EMT in colon cancer cells via TGF-β/Smad pathway.However,losartan can reverse the effects induced by angiotensin Ⅱ.The results of this study suggest that AT1 R may be a new targeted therapy site or pharmacological site for colon cancer patients.