Estrogen plays a critical role in AAV2-mediated gene transfer in ovarian cancer.

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.

• 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)

Chemical References

• Antiviral Agents
• Integrin alphaVbeta3
• Proteoglycans
• Receptors, Vitronectin
• heparin proteoglycan
• integrin alphaVbeta5
• Estradiol
• Heparin
• Ganciclovir

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