Molecular analysis of apoptosis pathway after photodynamic therapy in breast cancer: Animal model study

Luciana C Silva; Juliana Ferreira-Strixino; Letícia C Fontana; António M d'A Rocha Gonsalves; Arménio C Serra; Marta Pineiro; Renata A Canevari

doi:10.1016/j.pdpdt.2016.03.006

Molecular analysis of apoptosis pathway after photodynamic therapy in breast cancer: Animal model study

Photodiagnosis Photodyn Ther. 2016 Jun:14:152-8. doi: 10.1016/j.pdpdt.2016.03.006. Epub 2016 Mar 24.

Authors

Luciana C Silva¹, Juliana Ferreira-Strixino², Letícia C Fontana³, António M d'A Rocha Gonsalves⁴, Arménio C Serra⁴, Marta Pineiro⁴, Renata A Canevari⁵

Affiliations

¹ Instituto de Pesquisa e Desenvolvimento, IP&D-Laboratório de Biologia Molecular do Câncer and Laboratório de Espectroscopia Vibracional Biomédica, Universidade do Vale do Paraíba-UNIVAP, São José dos Campos, 12400-000, SP, Brazil.
² Instituto de Pesquisa e Desenvolvimento, IP&D-Laboratório de Terapia Fotodinâmica, Universidade do Vale do Paraíba-UNIVAP, São José dos Campos, 12400-000, SP, Brazil. Electronic address: juferreira@univap.br.
³ Instituto de Pesquisa e Desenvolvimento, IP&D-Laboratório de Terapia Fotodinâmica, Universidade do Vale do Paraíba-UNIVAP, São José dos Campos, 12400-000, SP, Brazil.
⁴ Chymiotechnon, Departamento de Química, Universidade de Coimbra, 3049-535, Coimbra, Portugal.
⁵ Instituto de Pesquisa e Desenvolvimento, IP&D-Laboratório de Biologia Molecular do Câncer and Laboratório de Espectroscopia Vibracional Biomédica, Universidade do Vale do Paraíba-UNIVAP, São José dos Campos, 12400-000, SP, Brazil. Electronic address: rcanevari@univap.br.

PMID: 27018246
DOI: 10.1016/j.pdpdt.2016.03.006

Abstract

Background: Molecular investigation of breast tumors has permitted better understanding about interaction of genes and pathways involved in tumor progression.

Objective: The aim of this study was to evaluate the association between genes belonging to the pathway of apoptosis with tumor response to photodynamic therapy.

Study design/materials and methods: The mammary tumors were induced in twenty-four Spraguey-Dawley female rats by oral gavage of 7,12-dimethylbenz(a)anthracene (8mg/Kg body weight). Animals were divided into three groups: G1 (normal tissue), G2 (tumors without treatment), G3 (animals euthanized 48h after treatment). The photosensitizer used was a chlorin, 5,15-bis-(2-bromo-5-hydroxyphenyl) chlorin in the dose of 8mg/kg for each animal. Light source of diode laser at a wavelength of 660nm, fluence rate of 100mW/cm, and light dose of 100J/cm was delivery to lesions for treatment. A sample from each animal was investigated by quantitative real time PCR using Rat Apoptosis RT(2) Profiler™ PCR Array platform.

Results: Pro-apoptotic BAK1, CARD6, CASP8, CIDEA, CIDEB, DAPK1, TNF, TNFRSF10B, FASLG, LOC687813, and TP73 genes showed increased expression, and CD40 anti-apoptotic gene showed decreased expression in the group who underwent PDT (G3) in relation to G2.

Conclusion: The results indicated that these genes are involved more directly with cellular apoptosis induced by PDT using the Chlorin photosensitizer.

Keywords: Apoptosis; Breast cancer; Chlorin; Photodynamic therapy.

MeSH terms

Animals
Apoptosis
Breast Neoplasms* / genetics
Breast Neoplasms* / therapy
Disease Models, Animal
Female
Gene Expression / drug effects
Gene Expression / radiation effects
Photochemotherapy*
Porphyrins / therapeutic use
Rats
Real-Time Polymerase Chain Reaction
Signal Transduction / radiation effects

Substances

Porphyrins
chlorin