[Killing effect of double suicide genes mediated by retroviral vector on k562 cells].
The aim of study was to investigate the killing effect of double suicide gene system mediated by retroviral vector on K562 cells in vivo and ex vivo. CDglyTK gene was transfected into PA317 cells by using lipofectamine. K562 cells were infected with viral supernatant. K562/CDglyTK cells were treated with 5-fluorocytosine (5-FC) and/or ganciclovir (GCV). Mice were randomly divided into three groups: tumor formation, tumor inhibition and tumor therapy. Each mouse was implanted with K562/CDglyTK cells or K562 cells. The results indicated that the killing effect of 5-FC in combination with GCV on K562/CDglyTK was more significant than using 5-FC or GCV alone. In vivo study showed that after being injected subcutaneously with K562 cells and K562/CDglyTK cells, there was not obvious difference in tumor formation rate of mice, 5-FC + GCV could suppress tumor formation of the K562/CDglyTK cells. After being treated with 5-FC and GCV, the median tumor volume of mice implanted with K562/CDglyTK cells decreased obviously, compared with the control group. Their median survival was significantly prolonged. It is concluded that double suicide genes are more effective for killing effect on K562 cells in vivo and in ex vivo. It may be applicable to clinical gene therapy.
Jiang
Yi-Rong
YR
Department of Hematology, The People Hospital of Dongguan, Dongguan 523018, China. jiangyirong1970@yahoo.com.cn
Lai
Ying-Chang
YC
Chen
Xiao-Lin
XL
Wan
De-Sheng
DS
Chen
Wan-Ning
WN
Qi
Miao-Hua
MH
Liu
Chun-Sheng
CS
Chen
Xue-Liang
XL
Ma
Dao-Xin
DX
D043525:Cytosine Deaminase / Q000235:genetics*; D005437:Flucytosine / Q000494:pharmacology; D015774:Ganciclovir / Q000494:pharmacology; D041722:Genes, Transgenic, Suicide / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D020014:K562 Cells; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics; D011995:Recombination, Genetic; D012190:Retroviridae / Q000235:genetics
D011993:Recombinant Fusion Proteins; D005437:Flucytosine; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D043525:Cytosine Deaminase; D015774:Ganciclovir