Ablative Hypofractionated Radiation Therapy Enhances Non-Small Cell Lung Cancer Cell Killing via Preferential Stimulation of Necroptosis In Vitro and In Vivo.
Int J Radiat Oncol Biol Phys
; 101(1): 49-62, 2018 05 01.
Article
em En
| MEDLINE
| ID: mdl-29619976
ABSTRACT
PURPOSE:
To investigate how necroptosis (ie, programmed necrosis) is involved in killing of non-small cell lung cancer (NSCLC) after ablative hypofractionated radiation therapy (HFRT). METHODS AND MATERIALS Deoxyribonucleic acid damage, DNA repair, and the death form of NSCLC cells were assessed after radiation therapy. The overexpression and silencing of receptor-interacting protein kinases 3 (RIP3, a key protein involved activation of necroptosis)-stable NSCLC cell lines were successfully constructed. The form of cell death, the number and area of colonies, and the regulatory proteins of necroptosis were characterized after radiation therapy in vitro. Finally, NSCLC xenografts and patient specimens were used to examine involvement of necroptosis after ablative HFRT in vivo.RESULTS:
Radiation therapy induced expected DNA damage and repair of NSCLC cell lines, but ablative HFRT at ≥10 Gy per fraction preferentially stimulated necroptosis in NSCLC cells and xenografts with high RIP3 expression, as characterized by induction and activation of RIP3 and mixed-lineage kinase domain-like protein and release of immune-activating chemokine high-mobility group box 1. In contrast, RNA interference of RIP3 attenuated ablative HFRT-induced necroptosis and activation of its regulatory proteins. Among central early-stage NSCLC patients receiving stereotactic body radiation therapy, high expression of RIP3 was associated with improved local control and progression-free survival (all P < .05).CONCLUSIONS:
Ablative HFRT at ≥10 Gy per fraction enhances killing of NSCLC with high RIP3 expression via preferential stimulation of necroptosis. RIP3 may serve as a useful biomarker to predict favorable response to stereotactic body radiation therapy.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
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Prevencao_e_fatores_de_risco
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Agentes_cancerigenos
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Tipos_de_cancer
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Pulmao
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Tratamento
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Radioterapia
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Pulmonar de Células não Pequenas
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Proteína Serina-Treonina Quinases de Interação com Receptores
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Hipofracionamento da Dose de Radiação
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Neoplasias Pulmonares
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Necrose
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Int J Radiat Oncol Biol Phys
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China