Ovarian cancer gene therapy using HPV-16 pseudovirion carrying the HSV-tk gene.
Ovarian cancer is the leading cause of death from all gynecological cancers and conventional therapies such as surgery, chemotherapy, and radiotherapy usually fail to control advanced stages of the disease. Thus, there is an urgent need for alternative and innovative therapeutic options. We reason t...
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doaj-6290ab8911e7467c8c747308f2aac03e2020-11-25T01:48:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0177e4098310.1371/journal.pone.0040983Ovarian cancer gene therapy using HPV-16 pseudovirion carrying the HSV-tk gene.Chien-Fu HungAn Jen ChiangHsiao-Hsuan TsaiMartin G PomperTae Heung KangRichard R RodenT-C WuOvarian cancer is the leading cause of death from all gynecological cancers and conventional therapies such as surgery, chemotherapy, and radiotherapy usually fail to control advanced stages of the disease. Thus, there is an urgent need for alternative and innovative therapeutic options. We reason that cancer gene therapy using a vector capable of specifically delivering an enzyme-encoding gene to ovarian cancer cells will allow the cancer cell to metabolize a harmless prodrug into a potent cytotoxin, which will lead to therapeutic effects. In the current study, we explore the use of a human papillomavirus (HPV) pseudovirion to deliver a herpes simplex virus thymidine kinase (HSV-tk) gene to ovarian tumor cells. We found that the HPV-16 pseudovirion was able to preferentially infect murine and human ovarian tumor cells when administered intraperitoneally. Furthermore, intraperitoneal injection of HPV-16 pseudovirions carrying the HSV-tk gene followed by treatment with ganciclovir led to significant therapeutic anti-tumor effects in murine ovarian cancer-bearing mice. Our data suggest that HPV pseudovirion may serve as a potential delivery vehicle for ovarian cancer gene therapy.http://europepmc.org/articles/PMC3398866?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chien-Fu Hung An Jen Chiang Hsiao-Hsuan Tsai Martin G Pomper Tae Heung Kang Richard R Roden T-C Wu |
spellingShingle |
Chien-Fu Hung An Jen Chiang Hsiao-Hsuan Tsai Martin G Pomper Tae Heung Kang Richard R Roden T-C Wu Ovarian cancer gene therapy using HPV-16 pseudovirion carrying the HSV-tk gene. PLoS ONE |
author_facet |
Chien-Fu Hung An Jen Chiang Hsiao-Hsuan Tsai Martin G Pomper Tae Heung Kang Richard R Roden T-C Wu |
author_sort |
Chien-Fu Hung |
title |
Ovarian cancer gene therapy using HPV-16 pseudovirion carrying the HSV-tk gene. |
title_short |
Ovarian cancer gene therapy using HPV-16 pseudovirion carrying the HSV-tk gene. |
title_full |
Ovarian cancer gene therapy using HPV-16 pseudovirion carrying the HSV-tk gene. |
title_fullStr |
Ovarian cancer gene therapy using HPV-16 pseudovirion carrying the HSV-tk gene. |
title_full_unstemmed |
Ovarian cancer gene therapy using HPV-16 pseudovirion carrying the HSV-tk gene. |
title_sort |
ovarian cancer gene therapy using hpv-16 pseudovirion carrying the hsv-tk gene. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
Ovarian cancer is the leading cause of death from all gynecological cancers and conventional therapies such as surgery, chemotherapy, and radiotherapy usually fail to control advanced stages of the disease. Thus, there is an urgent need for alternative and innovative therapeutic options. We reason that cancer gene therapy using a vector capable of specifically delivering an enzyme-encoding gene to ovarian cancer cells will allow the cancer cell to metabolize a harmless prodrug into a potent cytotoxin, which will lead to therapeutic effects. In the current study, we explore the use of a human papillomavirus (HPV) pseudovirion to deliver a herpes simplex virus thymidine kinase (HSV-tk) gene to ovarian tumor cells. We found that the HPV-16 pseudovirion was able to preferentially infect murine and human ovarian tumor cells when administered intraperitoneally. Furthermore, intraperitoneal injection of HPV-16 pseudovirions carrying the HSV-tk gene followed by treatment with ganciclovir led to significant therapeutic anti-tumor effects in murine ovarian cancer-bearing mice. Our data suggest that HPV pseudovirion may serve as a potential delivery vehicle for ovarian cancer gene therapy. |
url |
http://europepmc.org/articles/PMC3398866?pdf=render |
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