Amphiregulin Antisense RNA Delivered by Adnovirus Suppresses Growth of Breast Cancer Cells In Vitro and In Vivo  

作　　者：LinMa VoahangyRandrianarison FabienCalvo 

机构地区：[1]DepartmentofRadiotherapy,ChinesePLAGeneralHospital,Beijing100853,China [2]LaboratoiredeVectorologieetTransfertdeGénes,CNRSUMR1582,Villejuif94805,France. [3]LaboratoiredePharmacologieExpérimentaleetClinique,INSERMEPI-9932,Paris75010,France

出　　处：《Chinese Journal of Clinical Oncology》2005年第2期533-537,共5页中国肿瘤临床（英文版）

摘　　要：OBJECTIVE To investigate the therapeutic potential of amphiregulin antisense RNA delivered by adenoviral vector in a human breast cancer model.METGODS Human amphiregulin cDNA was subcloned in the opposite orientation to the cytomegaloviral promoter and inserted into an El/E3-deleted type 5 adenoviral vector to obtain an AdA4 construct which expresses amphiregulin antisense mRNA. Both in vitro and in vivo antiproliferative effects of the antisense RNA were studied by infecting transformed human breast epithelial NS2T2A1 cells and tumors.RESULTS Amphiregulin protein expression was inhibited dramatically in the NS2T2A1 cells after infection with AdA4. The in vitro cell growth was inhibited significantly at day 4 post-AdA4 infection compared with control empty virus AdCl at a MOI of 200 and 400 pfu/cell to 69.3% and 49.8%, respectively (P<0.02, P<0.005). After 3 intra-tumoral injections of 10^9 pfu AdA4, tumor volumes were reduced to 40.6% of that of the control group at day 35 (P<0.005).CONCLUSION The transfer of amphiregulin RNA antisense by adenoviral vector is effective for amphiregulin targeting strategy, leading to an inhibition of in vitro cell proliferation and in vivo tumor growth in this breast cancer model.

关 键 词：RNA传递 病理机制 胸腺癌 肿瘤细胞 

分 类 号：R737.9[医药卫生—肿瘤]