Abstract: Killing Effect of Lentivirus-mediated Double Suicide Genes on Human Breast CancerCells in vivoHeng KONG1, Zonghai HUANG2, Haijin CHEN2, Linyu TAO1, Ke QI1Corresponding author: Heng KONG, E-mail: generaldoc@126.com1Department of Breast and Thyroid Surgery, The Nanshan Hospital of Shenzhen City, Shenzhen 518052, China2Department of General Surgery, Zhujiang Hospital of Nanfang Medical University, Guangzhou 510282, ChinaThis work was supported by a grant from the National High Technology Research and Development Program of China (863 Program) (No. 2001AA217171 )Abstract Objective: To evaluate the killing effect of lentivirus mediated CD/TK fusion gene controlled by kinase insertdomain-containing receptor (KDR) promoter on human breast cancer cells in vivo. Methods: Nude mice were used as hosts for cellline MCF-7 xenografts to establish the animal model of breast cancer. The tumor-bearing mice were randomly divided into 4 groups.Group Ⅰ were blank controls with tumor-bearing mice with no treatment. Group Ⅱ was injected with lentivirus and prodrug ( 5-FC+GCV ). Group Ⅲ was injected with lentivirus. Group Ⅳ was injected with prodrug. Tumor growth rate, tumor size and weight wereobserved. The expression of double suicide genes in xenograft tumors was examined by RT-PCR. The tumor tissue was analyzed byhematoxylin-eosin staining and PCNA immunohistochemistry. Flow cytometry (FCM) was used for cell cycle analysis. Results: Tumorgrowth was obviously inhibited in group Ⅱ. But there was no significant difference in tumor growth among group Ⅰ, group Ⅲ, andgroup Ⅳ. RT-PCR demonstrated the existence of CD/TK gene in genetically modified xenograft tumor cells. The expression of PCNAwas lower in tumor tissue of group Ⅱ than in group Ⅰ. Flow cytometry analysis showed that the proportion of G1 phase cells wasincreased and the proportion of G2-M phase cells was decreased. Conclusion: Combined with the prodrug, FGW-KDRP-CD/TK cansignificantly inhibit the growth of implanted breast cancer cells in nude mice and cell cycle arrest, which may be related to its inhibitoryeffect on PCNA expression.Keywords Breast cancer; Suicide gene therapy; Lentivirus; Cell cycle; Proliferating cell nuclear antigen