Molecular analysis of apoptosis pathway after photodynamic therapy in breast cancer: Animal model study
Luciana C Silva1, Juliana Ferreira-Strixino2, Letícia C Fontana2
1Instituto 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.
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.
Insights
Photodynamic therapy (PDT) effectively targets breast tumors by modulating apoptosis-related genes. Increased expression of pro-apoptotic genes and decreased expression of anti-apoptotic genes were observed following PDT treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Breast tumor progression involves complex gene interactions.
- Understanding these pathways is crucial for developing effective therapies.
- Apoptosis plays a key role in tumor cell death.
Purpose of the Study:
- To investigate the association between apoptosis-related genes and tumor response to photodynamic therapy (PDT).
- To identify specific genes involved in PDT-induced apoptosis in breast tumors.
Main Methods:
- Mammary tumors were induced in Sprague-Dawley rats using 7,12-dimethylbenz(a)anthracene.
- Animals were divided into control and PDT-treated groups.
- Gene expression analysis was performed using quantitative real-time PCR on the Rat Apoptosis RT(2) Profiler™ PCR Array.
Main Results:
- PDT treatment led to increased expression of pro-apoptotic genes including BAK1, CASP8, TNF, and TP73.
- The anti-apoptotic gene CD40 showed decreased expression post-PDT.
- These gene expression changes indicate a significant modulation of apoptosis pathways by PDT.
Conclusions:
- The study identified specific genes directly involved in PDT-induced cellular apoptosis.
- The findings highlight the role of apoptosis modulation in the efficacy of chlorin-based PDT for breast tumors.
Related Concept Videos
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01:30Apoptosis