Amphiregulin Antisense RNA Delivered by Adnovirus Suppresses Growth of Breast Cancer Cells In Vitro and In Vivo |
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基金项目: | the Advanced Research Program France-China,国家自然科学基金 |
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摘 要: |
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关 键 词: | RNA传递 病理机制 胸腺癌 肿瘤细胞 |
收稿时间: | 3 September 2004 |
修稿时间: | 2 March 2005 |
Amphiregulin antisense RNA delivered by adnovirus suppresses growth of breast cancer cells in vitro and in vivo |
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Authors: | Lin Ma Voahangy Randrianarison Fabien Calvo |
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Institution: | 1. Department of Radiotherapy, Chinese PLA General Hospital, Beijing 100853,China 2. Laboratoire de Vectorologie et Transfert de Génes, CNRS UMR 1582, Villejuif 94805, France 3. Laboratoire de Pharmacologie Experi mentale et Clinique, INSERM EPI-9932,Paris 75010, France |
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Abstract: | OBJECTIVE To investigate the therapeutic potential of amphiregulin antisense RNA delivered by adenoviral vector in a human breast cancer model.METHODS Human amphiregulin cDNA was subcloned in the opposite orientation to the cytomegaloviral promoter and inserted into an E1/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 AdC1 at a MOl 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 109 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. |
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Keywords: | amphiregulin antisense adenovirus breast cancer |
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