Abstract #0807

Effects of Phosphatidylcholine-Specific Phospholipase C Inhibition on Tumour Growth, Metabolism and HER2 Expression in Preclinical Models of HER-2 Overexpressing Ovarian Cancer

Rossella Canese¹, Alessandro Ricci¹, Maria Elena Pisanu¹, Luisa Paris¹, Luisa Altabella¹, Emiliano Surrentino¹, Marina Bagnoli², Ludmila Liliac³, Anna Granata², Silvana Canevari², Delia Mezzanzanica², Egidio Iorio¹, Franca Podo¹

¹Istituto Superiore di Sanit, Rome, RM, Italy; ²Fondazione IRCCS Istituto Nazionale dei Tumori;, Milan, Mi, Italy; ³Morphofunctional Sciences - Histology , University of Medicine and Pharmacy, Iasi, Romania

The altered MRS choline profile of human epithelial ovarian cancer (EOC) cells was found to be associated with activation of both choline kinase and phosphatidylcholine-specific phospholipase C (PtdCho-PLC). Inhibition of the latter enzyme by D609 induced decreases in both in vitro cell proliferation and in vivo tumor growth. Quantitative in vivo MRI/MRS examinations and ex-vivo analyses showed marked decreases in the tCho content, increases in the mean T2 and ADC values and decreases in the Ki67 index and HER2 expression in a subset (three out of six) xenografts of SKOV3.ip cells in SCID mice, following intraperitoneal administration of D609.