Stratégies pro-apoptotiques appliquées au traitement photodynamique avec le Foscan® de modèles précliniques d'adénocarcinome humain

Abstract : In order to develop a proapoptotic strategy in Foscan®-mediated photodynamic therapy (PDT) an evaluation of the parameters that govern the modulation of photoinduced apoptosis was performed on preclinical model from human adenocarcinoma. Moderate apoptosis was measured in Foscan® photosensitised tumour cells in vitro. The mitochondrial pathway was assumed to be indirectly induced by Foscan®-PDT. Spheroids were used to investigate the influence of oxygen consumption, through the modulation of fluence rate, on the induction of apoptosis. By using a low fluence rate, an oxygen conservative regimen, we demonstrated an increase in the activation of caspase-3 induced by Foscan®-PDT. The modulation of photoinduced apoptosis by extending the incubation time of Foscan® with MCF-7 cells was further investigated. After 3h incubation, the photosensitizer was mainly localised in the endoplasmic reticulum (ER) and Golgi apparatus. Following irradiation, ER oxidative stress through the induction of the chaperon protein GRP78 was observed. Subsequent apoptotic mitochondria response and caspase activation were induced. After 24h incubation with Foscan®, the ER localisation of the photosensitizer was intensified. As results, an increase in GRP78 expression correlated with an increase in caspase-7 activation independently of the mitochondria response was obtained. After in vivo PDT, immunohistochemistry was applied on tissue sections to evaluate the activation of caspases -3 and -7. Caspase-3 activation was found predominant suggesting a caspase-3 mediated apoptotic pathway in HT29 tumours subjected to Foscan®-PDT.
Complete list of metadatas

Cited literature [245 references]  Display  Hide  Download

https://hal.univ-lorraine.fr/tel-01777281
Contributor : Administrateur Du Ccsd <>
Submitted on : Tuesday, April 24, 2018 - 4:16:32 PM
Last modification on : Thursday, April 26, 2018 - 1:28:00 AM

File

SCD_T_2008_0037_MARCHAL.pdf
Files produced by the author(s)

Identifiers

  • HAL Id : tel-01777281, version 1

Collections

Citation

Sophie Marchal. Stratégies pro-apoptotiques appliquées au traitement photodynamique avec le Foscan® de modèles précliniques d'adénocarcinome humain. Sciences agricoles. Université Henri Poincaré - Nancy 1, 2008. Français. ⟨NNT : 2008NAN10037⟩. ⟨tel-01777281⟩

Share

Metrics

Record views

16

Files downloads

12