Radioiodine therapy, the most effective form of systemic radiotherapy available, is currently useful only for thyroid cancer because
of the thyroid-specifi c expression of the human sodium iodide symporter (hNIS). Here, we explore the effi cacy of a novel form of
gene therapy using prostate-specifi c membrane antigen (PSMA) promoter-mediated hNIS gene transfer followed by radioiodine
administration for the treatment of castration-resistant prostate cancer (CRPC). The androgen-dependent C33 LNCaP cell line
and the androgen-independent C81 LNCaP cell line were transfected by adenovirus. PSMA promoter-hNIS (Ad.PSMApro-hNIS) or
adenovirus.cytomegalovirus–hNIS containing the cytomegalovirus promoter (Ad.CMV-hNIS) or a control virus. The iodide uptake
was measured in vitro. The in vivo iodide uptake by C81 cell xenografts in nude mice injected with an adenovirus carrying the
hNIS gene linked to PSMA and the corresponding tumor volume fl uctuation were assessed. Iodide accumulation was shown
in different LNCaP cell lines after Ad.PSMApro-hNIS and Ad.CMV-hNIS infection, but not in different LNCaP cell lines after
adenovirus.cytomegalovirus (Ad.CMV) infection. At each time point, higher iodide uptake was shown in the C81 cells infected with
Ad.PSMApro-hNIS than in the C33 cells (P < 0.05). An in vivo animal model showed a signifi cant difference in 131I radioiodine
uptake in the tumors infected with Ad.PSMApro-hNIS, Ad.CMV-hNIS and control virus (P < 0.05) and a maximum reduction of
tumor volume in mice infected with Ad.PSMApro-hNIS. These results show prostate-specifi c expression of the hNIS gene delivered
by the PSMA promoter and effective radioiodine therapy of CRPC by the PSMA promoter-driven hNIS transfection.

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