Anti-tumor Effects of Gene Therapy with GALV Membrane Fusion Glycoprotein in Lung Adenocarcinoma
- 204 Downloads
- 2 Citations
Abstract
This study examined the efficacy of gene therapy of lung adenocarcinoma using specifically controlled type I herpes simplex virus recombinant vector expressing Gibbon ape leukemia virus membrane fusion glycoprotein gene (GALV.fus). Recombinant HSV-I plasmid carrying target transgene was constructed, and recombinant viral vector was generated in Vero cells using Lipofectamine transfection. Viral vector was introduced into lung adenocarcinoma A549 cells or human fetal fibroblast HFL-I GNHu 5 cells, or inoculated into human lung adenocarcinoma xenografts in nude mice. The anti-tumor and cytotoxic effects of GALV-FMG, the transgene, were examined in these cell and animal models. Expression of GALV-FMG in xenographs achieved 100 % tumorigenicity. Recombinant HSV-I viral vector also exhibited significant tumor cell killing effect in vitro. Relative survival rates of tumor cells treated with GALV-FMG or control vectors were, respectively, 20 and 70 %. GALV.fus has a potent anti-tumor effect against lung cancer both in vitro and in vivo. This anti-tumor potential provides foundation for further studies with this vector.
Keywords
Type I herpes simplex virus Lung adenocarcinoma Gibbon ape leukemia Virus membrane fusion glycoprotein Gene therapyAbbreviations
- HSV-I
Herpes simplex virus type I
- GALV.fus
Gibbon ape leukemia virus membrane fusion glycoprotein
- CMV
Cytomegalovirus
- EGFP
Enhanced green fluorescent protein
- FBS
Fetal bovine serum
- DMEM
Dulbecco’s modified Eagle medium
- Tk
Thymidine kinase
Notes
Acknowledgments
This study was supported by the National Natural Sciences Foundation of China (Grant number 30471984), the Foundation of Bureau of Public Health of Chongqing (Grants 06-2-001 and 2010-2-127), and the project Innovation of Science and Technology, Chongqing Science and Technology Commission (project number: cstc2013jcyjA10108).
Conflict of interest
All authors declare no conflicts of interest.
References
- 1.Burton, E. A., Wechuck, J. B., Wendell, S. K., Goins, W. F., Fink, D. J., & Glorioso, J. C. (2001). Multiple applications for replication-defective herpes simplex virus vectors. Stem Cells, 19, 358–377.PubMedCrossRefGoogle Scholar
- 2.Faith, S. A., Sweet, T. J., Bailey, E., Booth, T., & Docherty, J. J. (2006). Resveratrol suppresses nuclear factor-kappaB in herpes simplex virus infected cells. Antiviral Research, 72, 242–251.PubMedCrossRefGoogle Scholar
- 3.Higuchi, H., Bronk, S. F., Bateman, A., Harrington, K., Vile, R. G., & Gores, G. J. (2000). Viral fusogenic membrane glycoprotein expression causes syncytia formation with bioenergetic cell death: implications for gene therapy. Cancer Research, 60, 6396–6402.PubMedGoogle Scholar
- 4.Cerovska, N. (2001). Culture and biochemical analysis of cells. In D. L. Spector, R. D. Goldman, & L. A. Leinwand (Eds.), Cells: A laboratory manual (Chinese ed., pp. 830–831). Beijing: Beijing Science Publishing House.Google Scholar
- 5.Rao, S., Lowe, M., Herliczek, T. W., & Keyomarsi, K. (1998). Lovastatin mediated G1 arrest in normal and tumor breast cells is through inhibition of CDK2 activity and redistribution of p21 and p27, independent of p53. Oncogene, 17, 2393–2402.PubMedCrossRefGoogle Scholar
- 6.Rao, S., Porter, D. C., Chen, X., Herliczek, T., Lowe, M., & Keyomarsi, K. (1999). Lovastatin-mediated G1 arrest is through inhibition of the proteasome, independent of hydroxymethyl glutaryl-CoA reductase. Proceedings of the National Academy of Sciences of the United States of America, 96, 7797–7802.PubMedCentralPubMedCrossRefGoogle Scholar
- 7.Zhang, J., Frolov, I., & Russell, S. J. (2004). Gene therapy for malignant glioma using Sindbis vectors expressing a fusogenic membrane glycoprotein. Journal of Gene Medicine, 6, 1082–1091.PubMedCrossRefGoogle Scholar
- 8.Fu, X., Meng, F., Tao, L., Jin, A., & Zhang, X. (2003). A strict-late viral promoter is a strong tumor-specific promoter in the context of an oncolytic herpes simplex virus. Gene Therapy, 10, 1458–1464.PubMedCrossRefGoogle Scholar
- 9.Martin, E. T., Koelle, D. M., Byrd, B., Huang, M. L., Vieira, J., Corey, L., et al. (2006). Sequence-based methods for identifying epidemiologically linked herpes simplex virus type 2 strains. Journal of Clinical Microbiology, 44, 2541–2546.PubMedCentralPubMedCrossRefGoogle Scholar