Inhibitory effect of pulmonary carcinoma by adenovirus-mediated CD/UPRT gene

Abstract

The cell killing effects and bystander effects of double suicide gene on pulmonary carcinoma cells were explored. Lung adenocarcinoma cells (A549) were transfected with different titers of adenovirus vector and followed with different concentrations of 5-FC after a recombinant adenovirus vector carrying CD/UPRT gene (Ad-CD/UPRT) was constructed. The cell viability was measured by MTT assay 4 days later. The cell viability was dropped to 30.57 %–8.62 % after 10 MOI of Ad-CD/UPRT transfected and 5-FC (10–1000 µg/mL) administration. Furthermore, Ad-CD/UPRT-infected A549 cells showed a profound neighbor cell killing effect in the same methods. These results suggested that Ad-CD/UPRT/5-FC system can effectively suppress growth of lung adenocarcinoma cells, which may provide a novel and powerful candidate for lung cancer gene therapy strategies.

Keywords

pulmonary carcinoma / adenovirus / suicide gene / gene therapy

References

[1] HeT. C., ZhouS., CostaL. T., et al.. A simplified system for generating recombinant adenovirus. Proc Natl Acad Sci USA, 1998, 95: 2509-2514

[2] KocchlinB. A., RubioF., PalmerS., et al.. The metabolism of 5-fluorocytosine-2-14-C and cytosine-14-C in the rat and the disposition of 5-fluorocytosine-2-14-C in man. Biochem Pharmacol, 1996, 15: 435-446

[3] YazawaK., FisherW. E., BrunicardiF. C.. Current progress in suicide gene therapy for cancer. World J Surg, 2002, 26(7): 783-789

[4] MiyagiT., KoshidaK., HoriO., et al.. Gene therapy for prostate cancer using the cytosine deaminase/uracil phosphoribosyltransferase suicide system. J Gene Med, 2003, 5(1): 30-37

[5] WuD. H., LiuL., ChenL. H.. Antitumor effects and radiosensitization of cytosine deaminase and thymidine kinase fusion suicide gene on colorectal carcinoma cells. World J Gastroenterol, 2005, 11(20): 3051-3055

[6] VolpersC., KochanekS.. Adenoviral vectors for gene transfer and therapy. J Gene Med, 2004, 6(Suppl1): S164-S171

[7] DennyW. A.. Tumor-activated prodrugs-a new approach to cancer therapy. Cancer Invest., 2004, 22(4): 604-619

[8] RamnaraineM., PanW., GoblirschM., et al.. Direct and bystander killing of sarcomas by novel cytosine deaminase fusion gene. Cancer Res, 2003, 63(20): 6847-6854