Adenoviral-delivered HE4-HSV-tk sensitizes ovarian cancer cells to ganciclovir
dc.contributor.author | Rawlinson, Jennifer W. | |
dc.contributor.author | Vaden, Kiara | |
dc.contributor.author | Hunsaker, Joseph | |
dc.contributor.author | Miller, David F. | |
dc.contributor.author | Nephew, Kenneth P. | |
dc.contributor.department | Department of Cellular & Integrative Physiology, IU School of Medicine | en_US |
dc.date.accessioned | 2016-07-19T16:06:29Z | |
dc.date.available | 2016-07-19T16:06:29Z | |
dc.date.issued | 2013 | |
dc.description.abstract | Ovarian cancer (OC) is most often contained within the peritoneal cavity, making it an ideal disease for adenoviral-delivered gene therapies. In effort to develop a safe and effective gene therapy for OC, we created a replication deficient adenovirus bearing the herpes simplex thymidine kinase (HSV-tk) gene under direction of the tumor specific promoter human epididymis protein 4 (HE4). The purpose of this study was to investigate the ability of our adenoviral construct to transduce OC cells in vitro and mediate transgene expression of HSV-tk, thereby sensitizing OC to the pro-drug ganciclovir. Cisplatin-sensitive (CS) and -resistant (CR) A2780 OC cells, infected with virus for 6 hours at 100, 500, and 1000 multiplicity of infection followed by ganciclovir treatment every other day for 5 days, were assayed for cell viability. Adenoviral-mediated transgene expression increased with increasing amounts of virus and peaked at 48 hours after transduction in both A2780-CS and -CR. Unexpectedly, ganciclovir alone was slightly toxic to both A2780 cell lines (IC50 of 234.9 μg/mL and 257.2 μg/mL in A2780-CS and -CR, respectively). Transduction with ADV-HE4-HSV-tk followed by ganciclovir treatment increased (P<0.05) cell killing up to ten-fold, lowering the IC50 to 23.9 μg/mL and 32.6 μg/mL in A2780-CS and -CR, respectively, at 1000 multiplicity of infection. The results support the potential use of this approach as a gene therapy for OC, a disease that accounts for more deaths than any other cancer of the female reproductive system. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Rawlinson, J. W., Vaden, K., Hunsaker, J., Miller, D. F., & Nephew, K. P. (2013). Adenoviral-delivered HE4-HSV-tk sensitizes ovarian cancer cells to ganciclovir. Gene Therapy & Molecular Biology, 15, 120–130. | en_US |
dc.identifier.issn | 1529-9120 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/10410 | |
dc.language.iso | en_US | en_US |
dc.publisher | Gene Therapy Press | en_US |
dc.relation.journal | Gene Therapy & Molecular Biology | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | adenovirus | en_US |
dc.subject | gene therapy | en_US |
dc.subject | herpes simplex virus thymidine kinase | en_US |
dc.subject | ovarian cancer | en_US |
dc.title | Adenoviral-delivered HE4-HSV-tk sensitizes ovarian cancer cells to ganciclovir | en_US |
dc.type | Article | en_US |