title: Tissue specific expression of suicide genes delivered by nanoparticles inhibits gastric carcinoma growth.
abstract: Developing an efficient and safe strategy to introduce a therapeutic gene into targeting cells in vivo is a key issue in cancer gene therapy nowadays. Novel non-viral gene carriers, such as nanoparticles, have been shown to be able to deliver DNA into cancer cells efficiently. Suicide gene therapy has been demonstrated to be effective in inhibiting tumor growth, however, the lack of tumor specificity limits its application in clinic. Developing a targeting system for suicide gene is an attractive strategy in cancer gene therapy. In this study, the CMV enhancer and carcinoembryonic antigen (CEA) promoter was fused to a chimeric suicide gene yCDglyTK. This construct was delivered into SGC7901 gastric cancer cells using calcium phosphate nanoparticles (CPNPs). The expression of yCDglyTK in SGC7901 cells was confirmed by RT-PCR and western blot. Immunofluorescence experiments showed that yCDglyTK is only expressed in CEA-positive cancer cells, but not in CEA-negative cells. The expression of yCDglyTK induced cancer cell death following the addition of the prodrug 5-FC, and also elicit "bystander effect" to kill the neighboring cells. Intratumoral injection of CPNP-yCDglyTK complex followed by administration of 5-FC produced marked regression in gastric cancer xenografts. Taken together, our study suggests that the combination of calcium phosphate nanoparticles and suicide gene therapy represents a novel approach for targeting gastric cancer gene therapy.
authors.affiliation: Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan Province P. R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.forename: Guiying
authors.initials: G
authors.lastname: Zhang
authors.forename: Yong-Heng
authors.initials: YH
authors.lastname: Chen
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Chen
authors.forename: Xionghao
authors.initials: X
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Peng
authors.forename: Mei Hua
authors.initials: MH
authors.lastname: Xu
authors.forename: Jian Wei
authors.initials: JW
authors.lastname: Yuan
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000517:prevention & control; D000818:Animals; D002130:Calcium Phosphates; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D003587:Cytomegalovirus / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D041722:Genes, Transgenic, Suicide / Q000235:genetics*; D015316:Genetic Therapy; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D036103:Nanotechnology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control; D014183:Transplantation, Heterologous
chemical_list: D002130:Calcium Phosphates; D004273:DNA, Neoplasm