Synergetic bitherapy in mice with xenografts of human prostate cancer using a methional mimic (METLICO) and an aldehyde dehydrogenase 3 inhibitor (MATE): systemic intraperitoneal (IP) and targeted intra-tumoral (IT) administration
|Published in||Current Medicinal Chemistry. 2009, vol. 16, no. 10, p. 1184-1191|
|Abstract||An intraperitoneal (IP) monotherapy in nu/nu mice with subcutaneous xenografts of a human prostate epithelial cancer cell line:DU145 was undertaken with an aldehyde dehydrogenase 3 inhibitor MATE, that is a potent apoptogen on (DU145) in culture but not on their human prostate epithelial normal counterparts  . Tumour growth was slowed down but treatment had to be done 5days/week. To try to potentiate the action of MATE in vivo, a bitherapy was undertaken based on the synergetic apoptotic effect that had been observed previously in culture on DU145 treated with a methional mimic METLICO and DIMATE, an inhibitor of ALDH1 and ALDH3 . The bitherapy with METLICO/MATE administered IP was as effective as the monotherapy with MATE alone by IP, but at a 2-fold lower dose of MATE and at a dose of METLICO that had no growth-inhibitory effect as a monotherapy . Hence there was definite synergism with bitherapy. To try to increase the efficacy of bitherapy, it was administered by the intra-tumoral (IT) route using the recently developed 20-bars-pressurized microinjection system from CERMA [16, 17]. IT administration of the bitherapy was indeed more effective than that by IP as regards tumour volumes are concerned. Histopathological analysis of IT-treated tumours confirmed that there were many necrotized zones but intact cells were still present. Approaches for treating a wider zone of tumour tissue by IT-bitherapy are discussed.|
|Keywords||Aldehyde Dehydrogenase/*antagonists & inhibitors — Aldehydes/administration & dosage/*chemistry/therapeutic use — Animals — *Biomimetics — Combined Modality Therapy — Drug Delivery Systems — Enzyme Inhibitors/administration & dosage/chemistry/*therapeutic use — Female — Humans — Injections, Intralesional — Injections, Intraperitoneal — Male — Mice — Mice, Nude — Molecular Structure — Morpholines/chemistry/*therapeutic use — Prostatic Neoplasms/*drug therapy/pathology — Quinazolines/chemistry/*therapeutic use — Tumor Burden|
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|HILTBRAND, E. et al. Synergetic bitherapy in mice with xenografts of human prostate cancer using a methional mimic (METLICO) and an aldehyde dehydrogenase 3 inhibitor (MATE): systemic intraperitoneal (IP) and targeted intra-tumoral (IT) administration. In: Current Medicinal Chemistry, 2009, vol. 16, n° 10, p. 1184-1191. https://archive-ouverte.unige.ch/unige:19540|