AD-Sur-EGFP is a replication deficient adenovirus which cannot replicate in tumor cells, initiating a limited
time of Survivin down regulation and cell apoptosis; on the contrary, ZD55-Sur-EGFP can selectively replicate in those cells, delivering Survivin shRNA and then lyses the cells. This explanation is further confirmed by MTT assay: during the first two days, the cell viabilities AMN-107 manufacturer in AD-Sur-EGFP group was lower than in ZD55-EGFP group, but after 2 days, the cell viability in ZD55-EGFP group became lower than AD-Sur-EGFP group because of the replication of oncolytic virus. Previous study has shown that adenovirus based RNAi against Survivin led to significant inhibition of Survivin expression and tumor growth in vivo [7]. Our xenograft
tumor model demonstrated that ZD55-Sur-EGFP has a more potent antitumor activity than that of ZD55-EGFP, AD-Sur-EGFP and AD-EGFP. Besides the direct anticancer effect of the oncolytic virus itself, the much more efficient Survivin shRNA delivering, gene silencing and induction of apoptosis contribute greatly to the potent antitumor activity. Conclusion In conclusion, the ZD55-Sur-EGFP has both the oncolytic ability and the capacity to deliver Survivin shRNA. This oncolytic adenovirus based Survivin RNA interference could efficiently reduce the cell growth, tumorigenicity and increase apoptosis of colorectal cancer cells, which offers a prospect of improvement in treatment of CRC, even a promising treatment Gemcitabine clinical trial for other human cancers. Acknowledgements This project is supported by grants from the National Natural Science Foundation of China (Nos. 30772547) and Doctoral Fund of Ministry of Education of China (No. 20060631013). We thank Key Laboratory of Opthalamology, Chongqing Medical University for equipments support. References 1. Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin 2005, 55: 74–108.INCB28060 CrossRefPubMed 2. Sah NK, Khan Z, Khan GJ, Bisen PS: Structural, functional and therapeutic biology of Survivin. Cancer Lett. 2006, 244 (2) : 164–171.CrossRefPubMed
3. Ambrosini G, Adida C, Altieri DC: A noble anti-apoptotic gene, Survivin, is expressed in cancer and lymphoma. Nat. Med 1997, 3: 917–921.CrossRefPubMed 4. Williams NS, Gaynor RB, Scoggin S, Verma U, Gokaslan T, Simmang C, Fleming J, Tavana D, Frenkel E, Becerra Gemcitabine mw Cl: Identification and validation of genes involved in the pathogenesis of colorectal cancer using cDNA microarrays and RNA interference. Clin Cancer Res 2003, 9: 931–46.PubMed 5. Yan H, Thomas J, Liu T, Raj D, London N, Tandeski T, Leachman SA, Lee RM, Grossman D: Induction of melanoma cell apoptosis and inhibition of tumor growth using a cell-permeable Survivin antagonist. Oncogene 2006, 25: 6968–74.CrossRefPubMed 6. Coma S, et al.: Use of siRNAs and antisense oligonucleotides against Survivin RNA to inhibit steps leading to tumor angiogenesis. Oligonucleotides 2004, 14: 100–1351.CrossRefPubMed 7. Uchida H, et al.