A proteoliposome containing apolipoprotein A-I mutant (V156K) enhances rapid tumor regression activity of human origin oncolytic adenovirus in tumor-bearing zebrafish and mice
- 162 Downloads
We recently reported that the efficiency of adenoviral gene delivery and virus stability are significantly enhanced when a proteoliposome (PL) containing apolipoprotein (apo) A–I is used in an animal model. In the current study, we tested tumor removal activity of oncolytic adenovirus (Ad) using PL-containing wildtype (WT) or V156K. Oncolytic Ad with or without PL was injected into tumors of zebrafish and nude mice as a Hep3B tumor xenograft model. The V156K-PL-Ad-injected zebrafish, group showed the lowest tumor tissue volume and nucleic acids in the tumor area, whereas injection of Ad alone did not result in adequate removal of tumor activity. Reactive oxygen species (ROS) contents increased two-fold in tumor-bearing zebrafish; however, the V156K-PL-Ad injected group showed a 40% decrease in ROS levels compared to that in normal zebrafish. After reducing the tumor volume with the V156K-PL-Ad injection, the swimming pattern of the zebrafish changed to be more active and energetic. The oncolytic effect of PL-Ad containing either V156K or WT was about two-fold more enhanced in mice than that of Ad alone 34 days after the injection. Immunohistochemical analysis revealed that the PL-Ad-injected groups showed enhanced efficiency of viral delivery with elevated Ad-E1A staining and a diminished number of proliferating tumor cells. Thus, the antitumor effect of oncolytic Ad was strongly enhanced by a PL-containing apoA-I and its mutant (V156K) without causing side effects in mice and zebrafish models.
Keywordsapolipoprotein A–I oncolytic adenovirus proteoliposome reconstituted high-density lipoproteins zebrafish
Unable to display preview. Download preview PDF.
- Hitt, M., Bett, A.J., Prevec, L., and Graham, F.L. (1994). Construction and propagation of human adenovirus vectors. Cell biology: a laboratory handbook. (Academic Press Inc. New York), pp. 479–490.Google Scholar
- Nusslein-Volhard, C., and Dahm, R. (2002). Zebrafish: A Practical Approach (Oxford University Press).Google Scholar
- Spitsbergen, J.M., Tsai, H.W., Reddy, A., Miller, T., Arbogast, D., Hendricks, J.D., and Bailey, G.S. (2000). Neoplasia in zebrafish (Danio rerio) treated with N-methyl-N′-nitro-N-nitrosoguanidine by three exposure routes at different developmental stages. Toxicol. Pathol. 28, 716–725.PubMedCrossRefGoogle Scholar
- Su, F., Kozak, K.R., Imaizumi, S., Gao, F., Amneus, M.W., Grijalva, V., Ng, C., Wagner, A., Hough, G., Farias-Eisner, G., et al. (2010). Apolipoprotein A–I (apoA-I) and apoA-I mimetic peptides inhibit tumor development in a mouse model of ovarian cancer. Proc. Natl. Acad. Sci. USA 107, 19997–20002.PubMedCrossRefGoogle Scholar