Angiogenesis is a complex biological process that is involved in tumorigenesis and progression.However,the molecular mechanistic of underlying angiogenesis remain largely unknown.In this study,we accessed the expression of angiogenesis related proteins by immunohistochemical staining of human tissue microarray which contains 72 adenoid cystic carcinoma(AdCC),12 pleomorphic adenoma(PMA)and 18 normal salivary gland(NSG)using digital pathological scancer and scoring system.We found the expression of p-S6S235/236(a downstream of mTOR),EGFR,p-Stat3T705,HIF-1α and PAI was significantly increased in AdCC as compared with PMA and(or)NSG(P<0.05).To our surprised,the expression of these proteins was not associated with pathological type of human AdCC(P>0.05).Correlation analysis of these proteins revealed that p-S6S235/236up regulates the expression of EGFR/p-Stat3T705(P<0.05)and HIF-1α/PAI(P<0.05).Moreover,the activation of p-S6S235/236,EGFR/p-Stat3T705 and HIF1 α/PAI associated with angiogenesis(CD34)and proliferation(Ki-67).Further more,target inhibition of mTOR by rapamycin effectively decreased tumor growth of ACC-M cell line nude mice xenograft and reduced the expression of p-S6S235/236,EGFR/p-Stat3T705 and HIF-1α/PAI.Taken together,these date revealed that mTOR signaling pathway regulates tumor angiogenesis by EGFR/p-Stat3T705 and HIF-1 α/PAI.Inhibition of mTOR by rapamycin could effectively reduced tumor growth.It is likely that mTOR inhibitors may be a potential candidate for treatment of AdCC.