Acta Pharmacologica Sinica 2008 December; 29 (12): 1440-1450; doi: 10.1111/j.1745-7254.2008.00894.x

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 α_υβ₃ and α_υβ₅ 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 17β-estradiol on ovarian cancer cell proliferation, HSPG, the expressions of integrins α_υβ₃ and α_υβ₅, 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 α_υβ₃ and α_υβ₅ between OVCAR-3 and SKOV-3ip; (2) that 17β-estradiol was shown to significantly stimulate cell proliferation and integrin β5 expression in certain ovarian cancer cell lines; and (3) integrin-targeted 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 17β-estradiol. Moreover, this RGD-modified rAAV2 exerted more efficient transduction in ovarian cancer cells in response to 17β-estradiol.

Conclusion: Our findings implied that A520/N584RGD_rAAV2 may offer great potential for ovarian cancer treatment in vivo.

Keywords: adeno-associated viral vector; gene transfer; ovarian cancer; estrogen