Treatment of Tumor in Mice by Oral Administration of Cytosine Deaminase Gene Carried in Live Attenuated Salmonella.

Abstract

To study the possibility of oral gene therapy using live attenuated Salmonella, eukaryotic expression vectors EGFPN1, pLCDSN were introduced into a live attenuated AraA(-) auxotrophic mutant of Salmonella typhimurium (SL3261) and were administered orally to BALB/c and C57BL/6 mice. After six weeks, these mice were challenged with 4T(1) and Lewis cancer cells. Until the tumors reached to about 10 mm in diameter, 5-fluorocytosine was given through intraperitoneal injection. Flow cytometry, confocal microscopy and PCR methods were used to detect the integration and expression of the genes. The inhibition of the tumor and the survival time of the mice were also investigated. Results showed that cytosine deaminase gene integration could be detected in almost all kinds of mice tissue. And the GFP expression was much stronger in spleen and tumor than in other tissues. Cytosine deaminase/5-fluorocytosine system had significant antitumoractivities in vivo. The anti-tumor activities of cytosine deaminase/5-fluorocytosine at 500 mg/kg on 4T(1) and Lewis carcinoma in BALB/c and C57BL/6 mice were more potent than the efficiency of 5-fluorouracil 10 mg/kg(P 0.05). Therefor, this experiment demonstrates the potential value of live attenuated Salmonella as carrier for oral gene therapy.

• Authors: Yu-Hua Li, Yong-Mei Xie, Kun-Yuan Guo, Hui Chen, Yi Wei, Jian-Sheng Huang, Da-Ming Ren
• Journal: Sheng wu hua xue yu sheng wu wu li xue bao Acta biochimica et biophysica Sinica (Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai)) Vol. 33 Issue 2 Pg. 233-237 ( 2001) ISSN: 0582-9879 [Print] China
• PMID: 12050817 (Publication Type: Journal Article)