Therapeutic effect of focal adhesion kinase gene silence on leukemia.
- Author:
Lü-Hong XU
1
;
Jian-Pei FANG
;
Wen-Jun WENG
;
Hong-Gui XU
;
Ya-Ting ZHANG
Author Information
1. Department of Pediatrics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Focal Adhesion Kinase 1;
genetics;
Gene Silencing;
Genetic Vectors;
Leukemia, Experimental;
genetics;
therapy;
Male;
Mice;
Mice, Inbred BALB C;
RNA Interference;
RNA, Small Interfering;
genetics;
Transfection
- From:
Journal of Experimental Hematology
2011;19(3):602-606
- CountryChina
- Language:Chinese
-
Abstract:
This study was aimed to investigate the effects of focal adhesion kinase (FAK) gene silence on leukemia cell growth, leukemogenesis and efficacy of chemotherapy drug. Vector containing lentiviral-FAK-shRNA was constructed and transfected into BCR/ABL-BaF3 leukemic cells, the cell growth and apoptosis were detected in vitro. The effect of FAK shRNA on leukemogenesis was studied in a murine model with leukemia. The apoptosis of leukemia cells and survival of leukemic mice treated by FAK shRNA combined with drug STI571 were monitored. The results showed that FAK gene expression was knocked down by lentiviral-FAK-shRNA. FAK gene silencing inhibited leukemia cell growth in vitro. The apoptosis test results showed that the percentages of Annexin V(+) cells in vector control group and FAK shRNA group were (3.46 ± 0.56)% and (7.3 ± 0.79)%, respectively, and the difference was statistically significant (p < 0.05). The mice in vector control group died at day 21 to 27, while the mice in FAK shRNA group died between day 52 and 60, and the difference was statistically significant (p < 0.05). Moreover, FAK gene silence combined with drug STI571 could enhance the apoptosis of leukemia cells and prolong survival time of leukemic mice. It is concluded that FAK gene silence inhibits leukemogenesis and promotes efficacy of chemotherapy drug on leukemia cells, indicating FAK gene silence may be considered as a new therapeutic strategy for leukemia.
