Proteomic analysis reveals mechanisms underlying increased efficacy of bleomycin by photochemical internalization in bladder cancer cells.
Mol Omics
; 19(7): 585-597, 2023 08 14.
Article
em En
| MEDLINE
| ID: mdl-37345535
ABSTRACT
Photochemical internalization (PCI) is a promising new technology for site-specific drug delivery, developed from photodynamic therapy (PDT). In PCI, light-induced activation of a photosensitizer trapped inside endosomes together with e.g. chemotherapeutics, nucleic acids or immunotoxins, allows cytosolic delivery and enhanced local therapeutic effect. Here we have evaluated the photosensitizer meso-tetraphenyl chlorine disulphonate (TPCS2a/fimaporfin) in a proteome analysis of AY-27 rat bladder cancer cells in combination with the chemotherapeutic drug bleomycin (BML). We find that BLMPCI attenuates oxidative stress responses induced by BLM alone, while concomitantly increasing transcriptional repression and DNA damage responses. BLMPCI also mediates downregulation of bleomycin hydrolase (Blmh), which is responsible for cellular degradation of BLM, as well as several factors known to be involved in fibrotic responses. PCI-mediated delivery might thus allow reduced dosage of BLM and alleviate unwanted side effects from treatment, including pulmonary fibrosis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fotoquímica
/
Neoplasias da Bexiga Urinária
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Bleomicina
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Proteômica
Limite:
Animals
Idioma:
En
Revista:
Mol Omics
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Noruega