Maspin is a member of the
serine protease inhibitors and the
maspin gene, a tumor suppressor gene, is down-regulated in a large fraction of
prostate cancers. We evaluated the use of adeno-associated virus (AAV, serotype 2) vector encoding
maspin as a means for in vivo gene therapy for human
prostate cancer. TUNEL assay of subcutaneously formed LNCaP or DU145
tumors in nude mice showed that intratumoral AAV-mediated
maspin expression significantly upregulated the number of apoptotic cells compared with AAV-LacZ treatment. Immunofluorescence double staining for
maspin protein and apoptosis in LNCaP
tumors showed that the percentage of apoptotic cells in AAV-
maspin-mediated
maspin-expressing cells was significantly high compared with that in AAV-GFP-mediated GFP-expressing cells. Moreover, significantly fewer CD31-positive microvessels were observed in AAV-
maspin-treated
tumors compared with the control
tumors. These therapeutic responses were highly correlated to persistent
maspin expression in
tumors, confirmed by Western blot analysis until at least day 56
after treatment. Finally, intratumoral delivery of AAV-
maspin significantly suppressed growth of LNCaP and DU145
tumors and improved survival of mice. We conclude that AAV-mediated prolonged
maspin expression efficiently suppresses human prostate
tumor growth in vivo by apoptosis induction and inhibition of angiogenesis.