Received 17 September 2009; received in revised form 26 November 2009; accepted 27 November 2009. published online 15 January 2010.
Abstract
Background and aim
We investigated the anti-tumor effect induced by the combination of the radiotherapeutic agent 131I-RC-160 and the prodrug 5-FC in human non-small cell lung cancer (NSCLC) A549 cells that were co-expressing the human somatostatin receptor 2 gene (hSSTR2) and E. coli cytosine deaminase gene (CD).
Methods
We cloned both hSSTR2 and CD into a bicistronic mammalian expression plasmid and stably transfected it into A549 cells (pCIS-A549 cells). After antibiotic selection, SSTR expression in stable clones was determined by reverse transcription and polymerase chain reaction (RT-PCR), Western blot, flow cytometry and immunofluorescence analyses. To assess the in vivo targeting efficiency of the “engineered” A549 cells, the cells were subcutaneously injected into nude mice and the biodistribution of 99mTc-RC-160 was assessed at different time points. The tumor inhibitory effects of 131I-RC-160 and/or 5-FC were evaluated by measurement of tumor growth and immunohistochemical analysis.
Results
Multiple analyses demonstrated the successful expression of hSSTR2 in A549 cells. In vivo radioimaging revealed specific targeting of RC-160 to the tumors derived from pCIS-A549 cells when compared to those from control A549 cells. The tumor inhibitory rate of pCIS-A549 tumors in the 131I-RC-160 plus 5-FC-treated group was significantly higher than that in the single agent-treated group, control group and control tumors.
Conclusion
Co-expression of the hSSTR2 and CD genes in tumor cells can selectively sensitize these cells to the infra-additive effects of radioisotope-labeled RC-160 and 5-FC in vivo. This approach offers a potential therapeutic strategy for the treatment of lung cancer.
ABSTRACT