Surfactant Protein B Suppresses Lung Cancer Progression by Inhibiting Secretory Phospholipase A2 Activity and Arachidonic Acid Production.
Cell Physiol Biochem
; 42(4): 1684-1700, 2017.
Article
en En
| MEDLINE
| ID: mdl-28743125
ABSTRACT
BACKGROUND/AIMS:
Radiotherapy is applied to patients with inoperable cancer types including advanced stage non-small cell lung cancer (NSCLC) and radioresistance functions as a critical obstacle in radiotherapy. This study was aimed to investigate the mechanism of radioresistance regulated by surfactant protein B (SP-B).METHODS:
To investigate the role of SP-B in radioresistance, ΔSFTPB A549 cell line was established and SP-B expression was analyzed. In response to ionizing radiation (IR), the change of SP-B expression was analyzed in A549 and NCI-H441 cell lines. Conditioned media (CM) from NSCLC cells were utilized to evaluate the downstream signaling pathway. The in vivo effects of SP-B were assessed through mouse xenograft model with intratumoral injection of CM.RESULTS:
In response to IR, NSCLC cell lines showed decreased SP-B regulated by the TGF-ß signaling and decreased SP-B stimulated cell survival and epithelial-mesenchymal transition. Treatment with CM from irradiated cells activated sPLA2, enhanced protein kinase Cδ-MAPKs signaling pathway, and increased arachidonic acid production. We confirmed the in vivo roles of SP-B through mouse xenograft model.CONCLUSION:
Our results revealed that down-regulation of SP-B was involved in the radiation-induced metastatic conversion of NSCLC and provided evidence that SP-B acted as a suppressor of NSCLC progression.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Regulación Neoplásica de la Expresión Génica
/
Ácido Araquidónico
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Carcinoma de Pulmón de Células no Pequeñas
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Proteína B Asociada a Surfactante Pulmonar
/
Fosfolipasas A2 Secretoras
/
Neoplasias Pulmonares
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Cell Physiol Biochem
Asunto de la revista:
BIOQUIMICA
/
FARMACOLOGIA
Año:
2017
Tipo del documento:
Article