Treatment of Tumor in
Mice by Oral Administration of Cytosine Deaminase Gene Carried in Live
Attenuated Salmonella
LI Yu-Hua1,2, XIE Yong-Mei2, GUO
Kun-Yuan1*,�–HEN Hui2
WEI Yi2, HUANG Jian-Sheng2, REN Da-Ming 2
( 1Department of Hematology, Zhujiang
Hospital, First Military Medical University, Guangzhou 510282, China；2State Key Laboratory of
Genetic Engineering, Institute of Genetics, School of Life Science, Fudan
University, Shangshai 200433,
China )
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 4T1 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 4T1 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.
Key words cytosine deaminase； attenuated Salmonella； oral administration； tumor
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