RESUMEN
Radiation pneumonitis and pulmonary fibrosis are the main complications with radiotherapy for thoracic neoplasms, directly limiting the efficient dose in clinical application and currently there are few medicines that effectively function as radioprotectants. However, a TLR5 agonist, CBLB502, was confirmed to have protective efficacy against hematopoietic and gastrointestinal radiation syndromes in mice and primates. This study points to a new direction for protection against thoracic radiation-induced pulmonary syndromes and skin injury by CBLB502. We utilized the TUNEL assay, pathological analysis and immunohistochemistry to obtain evidence that CBLB502 could alleviate the occurrence of radiation pneumonitis and pulmonary fibrosis as well as radiation- induced skin injury. It may thus play a promising role in facilitating clinical radiotherapy of thoracic neoplasms.
Asunto(s)
Péptidos/uso terapéutico , Fibrosis Pulmonar/prevención & control , Traumatismos Experimentales por Radiación/prevención & control , Neumonitis por Radiación/prevención & control , Protectores contra Radiación/uso terapéutico , Receptor Toll-Like 5/agonistas , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Laminina/metabolismo , Pulmón/efectos de la radiación , Masculino , Ratones , Ratones Endogámicos C57BL , Péptidos/farmacología , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Proteína B Asociada a Surfactante Pulmonar/metabolismo , Traumatismos Experimentales por Radiación/metabolismo , Traumatismos Experimentales por Radiación/patología , Neumonitis por Radiación/metabolismo , Neumonitis por Radiación/patología , Protectores contra Radiación/farmacología , Úlcera Cutánea/etiología , Úlcera Cutánea/prevención & control , Receptor Toll-Like 5/metabolismoRESUMEN
The purpose of this study was to examine the effect of a Toll-like receptor 5 (TLR5) agonist, CBLB502, on the growth and radiosensitivity of A549 lung cancer cells in vivo. Expression of myeloid differentiation factor 88 (MyD88) or TLR5 was stably knocked down in human lung cancer cells (A549) using lentivirus expressing short hairpin RNA targeting human MyD88 or TLR5. Lack of MyD88 or TLR5 expression enhanced tumor growth in mouse xenografts of A549 lung cancer cells. CBLB502 inhibited the growth of A549 lung cancer cells, not A549-MyD88-KD cells in vivo in the murine xenograft model. Our results showed that the inhibition of A549 by CBLB502 in vivo was realized through regulating the expression of neutrophil recruiting cytokines and neutrophil infiltration. Finally, we found that activation of TLR5 signaling did not affect the radiosensitivity of tumors in vivo.
