Abstract
Objective
To evaluate transduction efficiency with recombinant adenovirus-mediated p53 (rAd/p53) therapy in a human colon cancer mouse model by intra-tumoral injection and intra-arterial delivery.
Methods
The tumor pieces of human colon cancer SW480 were implanted in the livers of 45 nude mice. These mice were administrated with rAd/p53 by intratumoral injection and intra-arterial delivery. After 24 h, 48 h and 72 h rAd/p53 administration, 5 mice each group were killed with over anesthesia and their livers were removed. P53 expression and apoptosis of tumor and liver were assessed.
Results
P53 expression and apoptosis of intratumoral administration group was higher than tail vein group and control group. Apoptosis and p53 expression of livers in three groups had no significant difference.
Conclusion
p53 gene transduction efficiency and anticancer effect of rAd/p53 is much better by intra-tumoral injection than intra-arterial delivery.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Baek JH, Agarwal ML, Tubbs RR, et al. In vivo recombinant adenovirus-mediated P53 gene therapy in a syngeneic rat model for colorectal cancer. J Korean Med Sci, 2004, 19: 831–841.
Tamm I, Schumacher A, Karawajew L, et al. Adenovirus-mediated gene transfer of P16INK/CDKN2 into bax-negative colon cancer cells induces apoptosis and tumor regression in vivo. Cancer Gene Ther, 2002, 9: 641–650.
Shimada H, Shimizu T, Ochai T, et al. Preclinical study of adenoviral p53 gene therapy for esophageal cancer. Surg Today, 2001, 31: 597–604.
Kim YI, Chung JW, Park JK, et al. Intraarterial gene delivery in rabbit hepatic tumors: transfection with nonviral vector by using iodized oil emulsion. Radiology, 2006, 240: 771–777.
Hannay, Davas JJ, Yu D, et al. Isolated limb perfusion: a noval delivery system for wild-type p53 and fiber-modified oncolytic adenoviruses to extremity sarcoma. Gene Ther, 2007, 14: 671–681.
Chung YL, Troy H, Banerji U, et al. Magnetic resonance spectroscopic pharmacodynamic markers of the heat shock protein 90 inhibitor 17-allylamino, 17-demethoxygeldanamycin (17AAGA) in human colon cancer models. J Natl Cancer Inst, 2003, 95: 1624–1633.
Ohashi M, Kanai F, Tateishi K, et al. Target gene therapy for α-Fetoprotein-producing hepatocellular carcinoma by E1B55k-attenuated adenovirus. Biochem Biophys Res Commun, 2001, 282: 529–535.
Block A, Freund CT, Chen SH, et al. Gene therapy of metastatic colon carcinoma: regression of multiple hepatic metastases by adenoviral expression of bacterial cytosine deaminase. Cancer Gene Ther, 2000, 7: 438–445.
Wang W, El-Deiry WS. Bioluminescent molecular imaging of endogenous exogenous p53-mediated transcription in vitro and in vivo using an HCT116 human colon carcinoma xenograft model. Cancer Biol Ther, 2003, 2: 196–202.
Tomayko MM, Reynolds CP. Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemother Pharmacol, 1989, 24: 148–154.
Okimoto T, Yahata H, Itou H, et al. Safety and growth suppressive effect of intra-hepatic arterial injection of AdCMV-p53 combined with CDDP to rat liver metastatic tumors. J Exp Clin Cancer Res, 2003, 22: 399–406.
Abe T, Wakimoto H, Bookstein R, et al. Intra-arterial delivery of p53-containing adenoviral vector into experimental brain tumors. Cancer Gene Ther, 2002, 9: 228–235.
Shimada H, Matsubara H, Shiratori T, et al. Phase I/II adenoviral p53 gene therapy for chemoradiation resistant advanced esophageal squamous cell carcinoma. Cancer Sci, 2006, 97: 554–561.
Guan YS, Sun L, Zhou XP, et al. Intratumoral injection of recombinant adenovirally-mediaed p53 (rAd/p53) gene combined with transcatheter arterial embolization for treatment of primary hepatic carcinoma. World J Digestol (Chinese), 2005, 13: 125–127.
Tada M, Hatano E, Taura K, et al. High volume hydrodynamic injection of gene expression in rat hepatic artery results in a high level of gene expression in rat hepatocellular carcinoma induced by diethylnitrosamine. J Gene Med, 2006, 8: 1018–1026.
Guan YS, Liu y, Zhou XP, et al. p53 gene (Gendicine) and embolisation overcome recurrent hepatocellular carcinoma. World J Gastroenterol, 2005, 11: 3803–3805.
Menon AG, Kuppen PJK, Burg SH van der, et al. Safety of intravenous administration of a canarypox virus encoding the human wild-type p53 gene in colorectal cancer patients. Cancer Gene Therapy, 2003, 10:509–517.
Roth JA. Adenovirus p53 gene therapy. Expert Opin Biol Ther, 2006, 6: 55–61.
Guan YS, La Z, Yang L, et al. p53 gene in treatment of hepatic carcinoma: status quo. World J Gastroenterol, 2007, 13: 985–992.
Kim JW, Lee HS. Tumor targeting by doxorubicin-RGD-4C peptide conjugate in an orthotopic mouse hepatoma model. Int J Mol Med. 2004, 14: 529–535.
Heise C, Sampson-Johannes A, Williams A, et al. ONYX-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherapeutic agents. Nat Med, 1997, 3: 639–645.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by grants from Guangzhou Health Agency (No. 2008-YB-034) and Guangdong Department of Science and Technology (No. 83083).
Rights and permissions
About this article
Cite this article
Xie, Q., Liang, B., Zhang, J. et al. In vivo comparison of transduction efficiency with recombinant adenovirus-mediated p53 in a human colon cancer mouse model by different delivery routes. Chin. -Ger. J. Clin. Oncol. 7, 704–708 (2008). https://doi.org/10.1007/s10330-008-0123-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10330-008-0123-y