Abstract | AIM: The aim of our study was to develop an effective gene delivery system for ovarian cancer gene therapy. METHODS: The expression of heparin sulfate proteoglycan ( HSPG) and integrins alpha(upsilon)beta(3) and alpha(upsilon)beta(5) were analyzed with flow cytometry on 2 human ovarian cancer cell lines (OVCAR-3 and SKOV-3ip). The gene transduction efficiencies were evaluated with recombinant adeno-associated viral vector (rAAV)2-green fluorescent protein or rAAV2-lactase Z followed by flow cytometry or cytohistochemistry staining. The effect of 17beta-estradiol on ovarian cancer cell proliferation, HSPG, the expressions of integrins alpha(upsilon)beta(3) and alpha(upsilon)beta(5), and adeno-associated viral vector (AAV)2-mediated gene transduction were determined. RESULTS: In the present study, we found: (1) a variation in HSPG and the expressions of integrins alpha(upsilon)beta(3) and alpha(upsilon)beta(5) between OVCAR-3 and SKOV-3ip; (2) that 17beta-estradiol was shown to significantly stimulate cell proliferation and integrin beta(5) expression in certain ovarian cancer cell lines; and (3) integrintargeted A520/N584RGD-rAAV2, which has alternative interactivity with integrins and abrogates the binding capacity HSPG, showed much higher gene transduction efficiency in ovarian cancer cells than rAAV2 in the presence/absence of 17beta-estradiol. Moreover, this RGD-modified rAAV2 exerted more efficient transduction in ovarian cancer cells in response to 17beta-estradiol. CONCLUSION: Our findings implied that A520/N584RGD-rAAV2 may offer great potential for ovarian cancer treatment in vivo.
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Authors | Wen-fang Shi, Jeffrey S Bartlett |
Journal | Acta pharmacologica Sinica
(Acta Pharmacol Sin)
Vol. 29
Issue 12
Pg. 1440-50
(Dec 2008)
ISSN: 1745-7254 [Electronic] United States |
PMID | 19026163
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antiviral Agents
- Integrin alphaVbeta3
- Proteoglycans
- Receptors, Vitronectin
- heparin proteoglycan
- integrin alphaVbeta5
- Estradiol
- Heparin
- Ganciclovir
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Topics |
- Animals
- Antiviral Agents
(pharmacology)
- Cell Death
(physiology)
- Cell Line, Tumor
(drug effects)
- Dependovirus
(genetics, metabolism)
- Estradiol
(metabolism)
- Female
- Ganciclovir
(pharmacology)
- Gene Transfer Techniques
- Genetic Therapy
- Genetic Vectors
(genetics, metabolism)
- Heparin
(analogs & derivatives, metabolism)
- Humans
- Integrin alphaVbeta3
(genetics, metabolism)
- Ovarian Neoplasms
(genetics, metabolism, therapy)
- Proteoglycans
(metabolism)
- Receptors, Vitronectin
(genetics, metabolism)
- Transduction, Genetic
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