Utilisation de nouveaux photosensibilisateurs pour le traitement du cancer de la prostate par photothérapie dynamique : Etude in vitro et in vivo

Abstract : Prostate cancer is the most frequently diagnosed cancer among men aged 50 years and older in industrialized countries. Medical research developed methods of focal therapy to treat this type of cancer conservatively and not radically in order to improve the patients quality of life. With this in mind, photodynamic therapy (PDT) is based on the use of photosensitizers (PS) able to specifically target cancer cells and, once activated by light, induce cell death. Based on Green Chemistry, the Laboratoire de Chimie des Substances Naturelles (LCSN) from Limoges developed new PS: protoporphyrin IX, a PS widely studied, vectorized with polyamines (PA). The effects of spermidine-linked protoporphyrin IX (PpIX-dSd) and spermine-linked protoporphyrin IX (PpIX-dSm) were studied on human prostate cancer cells PC-3, DU145 and LNCaP. This study demonstrated that both PS have the expected ideal properties: a pure composition, no toxicity in dark and ability to specifically target tumor cells. Moreover, PpIX-PA induced apoptotic intrinsic pathway. In addition, pathways involved in apoptosis resistance were studied: PS inhibited Bcl-2, Akt, NF-¦ÊB and autophagy but activated p38/COX-2/PGE2 pathway which was not involved in apoptosis resistance in our model. Finally, in vivo experiments showed PpIX-PA efficiency using subcutaneous xenograft of PC-3 cells performed on nude mice. Thus, these derivatives of PpIX-PA appear to be good candidates in prostate cancer treatment by PDT.
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Chloë Fidanzi-Dugas. Utilisation de nouveaux photosensibilisateurs pour le traitement du cancer de la prostate par photothérapie dynamique : Etude in vitro et in vivo. Médecine humaine et pathologie. Université de Limoges, 2016. Français. ⟨NNT : 2016LIMO0085⟩. ⟨tel-01435144⟩

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