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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.

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Keywords

abnormal according acquiring activation activity aggressive allowed altered analyses animals anticancer association attention binding biological biomedical biopsies block cancer cell cells choline coil combination confirmed content control controlling cultured daily days decrease decreases deprivation derived described detection discovery domains enhanced enzyme enzymes epithelial equipment established evidence evidenced examinations exerted exposed expression extracts features gradient growth hallmark health histological histology human immunodeficient implantation in vivo index indicators inhibition inhibitor injection investigations lipid localization maintenance manuscript maria marked measured medicine metabolic metabolism mice ministry model models moderate molecular moreover mouse nature oncology operating ovarian overall parental partial passage passaged pattern pharmacy phenotype play post potential preliminary preparation press program proliferation protocol quantitative raft rafts ranging rapid reduced reduction reported resolution response role saline sciences score sections selection separation serum special spectral staining starting status strong subset sucrose suggest support surface system table target targets thank tissue treated treatment tumor twice untreated vitro volume volumes warrants