방사선의학 웹진

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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-β 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.​ 

Lee S1, Kim D1, Kang J1, Kim E1, Kim W2, Youn H3, Youn B1,4.

Author information

1 Department of Integrated Biological Science, Pusan National University, Busan, Republic of Korea.

2 Integrative Graduate Program of Ship and Offshore Plant Technology for Ocean Energy Resource, Pusan National University, Busan, Republic of Korea.

3 Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul, Republic of Korea.

4 Department of Biological Sciences, Pusan National University, Busan, Republic of Korea.