PURPOSE: This study aimed to develop an efficient and safe strategy to introduce suicide genes into colon cancer cells. EXPERIMENTAL DESIGN: In this study, we fused an enhanced carcinoembryonic antigen promoter (CEA) to a suicide gene, cytosine deaminase (CD). This construct was delivered into colon cancer cells using calcium phosphate nanoparticles (CPNP). The cells were then treated with the prodrug 5-FC. The therapeutic effect was evaluated in vitro and in vivo. RESULTS: Our study showed that the CEA promoter-driven, CPNP-delivered suicide gene was only expressed in CEA-positive colon cancer cells, and resulted in significant cytotoxicity after administration of the prodrug 5-FC in vitro. Moreover, our in vivo study showed that CPNP-mediated CEA-CD delivery, together with 5-FC treatment, resulted in significant tumor growth delay in xenograft human colon carcinoma. CONCLUSIONS: Our study indicates that the combination of CPNP and CEA-CD gene expression represents a novel approach for CEA-positive tumor gene therapy.
PURPOSE: This study aimed to develop an efficient and safe strategy to introduce suicide genes into colon cancer cells. EXPERIMENTAL DESIGN: In this study, we fused an enhanced carcinoembryonic antigen promoter (CEA) to a suicide gene, cytosine deaminase (CD). This construct was delivered into colon cancer cells using calcium phosphate nanoparticles (CPNP). The cells were then treated with the prodrug 5-FC. The therapeutic effect was evaluated in vitro and in vivo. RESULTS: Our study showed that the CEA promoter-driven, CPNP-delivered suicide gene was only expressed in CEA-positive colon cancer cells, and resulted in significant cytotoxicity after administration of the prodrug 5-FC in vitro. Moreover, our in vivo study showed that CPNP-mediated CEA-CD delivery, together with 5-FC treatment, resulted in significant tumor growth delay in xenograft humancolon carcinoma. CONCLUSIONS: Our study indicates that the combination of CPNP and CEA-CD gene expression represents a novel approach for CEA-positive tumor gene therapy.
Authors: Lai Sum Leoh; Kouki Morizono; Kathleen M Kershaw; Irvin S Y Chen; Manuel L Penichet; Tracy R Daniels-Wells Journal: J Gene Med Date: 2014 Jan-Feb Impact factor: 4.565
Authors: Raúl Ortiz; José Prados; Consolación Melguizo; José L Arias; M Adolfina Ruiz; Pablo J Alvarez; Octavio Caba; Raquel Luque; Ana Segura; Antonia Aránega Journal: Int J Nanomedicine Date: 2012-01-09