Effects Of AngiotensinⅡ And Losartan On Cellular Growth And Expression Of VEGF And MCP-1in Human Pancreatic Cancer Cell Line SW1990

Objective:To investigate the effects of angiotensin Ⅱ（Ang Ⅱ） andangiotensinⅡ type1receptor （AT1R） blocker,Losartan,on the cellular growth and expression of vascularendothelial growth factor （VEGF） and monocyte chemoattractant protein1（MCP-1）mRNA and protein in human pancreatic cancer cell line SW1990.Methods:Cultured SW1990cells were treated by Ang Ⅱand Losartan with variousconcentrations and were collected at different time points. The proliferation was detectedby Cell Counting Kit-8（CCK8）;the apoptosis ratioes and changes of cell cycle weredetected by flow cytometry;the expression of AT1R、VEGF and MCP-1mRNA and proteinin cultured SW1990was determined by relative quantitative reverse transcriptionpolymerase chain reaction （RT-PCR）and enzyme-linked immunosorbent assay （ELISA）.Results:（1）Ang Ⅱ could stimulate the proliferation of SW1990cells, and the effect wasdose-and time-dependent. When the concentration of AngⅡ was10^-7mol/L and the timewas48hours, the effect reached the maximum,and which could be suppressed in dose-dependent manner by AT1R blocker,Losartan（P<0.05）.（2）The early stage apoptosis ofSW1990cells was detected by flow cytometry after they were incubated48hours withLosartan.Meanwhile,the ratio of G1phase was increased and the ratio of S phase and G2phase was decreased（P<0.05）.（3） AngⅡ could dose-dependently enhance the expressionof VEGF and MCP-1mRNA significantly after SW1990cells were incubated48hours.Aslo Ang Ⅱ could time-dependently enhance the expression of AT1RmRNA（P<0.05）.And which were all could be suppressed in dose-dependent manner by AT1Rblocker,Losartan（P<0.05）.（4） The levels of VEGF and MCP-1proteins was upregulatedsignificantly，which was dose-and time-dependent，after SW1990cells were incubated24and48hours with AngⅡ.And which were all could be suppressed in dose-dependent manner by AT1R blocker,Losartan （P<0.05）.Conclusions:（1）Ang Ⅱ stimulated the proliferation of SW1990cells, which was dose-andtime-dependent,and which could be suppressed in dose-dependent manner by AT1Rblocker, Losartan.The mechanisms may directly inhibit tumor cells proliferation,arrest cellcycle in resting stage,induce early stage apoptosis.（2）The expression of VEGF and MCP-1mRNA and protein can be induced by Ang Ⅱin human pancreatic cancer cell line throughAT1R, which may play a definite role in tumor growth and metastasis.