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Combining radiation with PI3K isoform-selective inhibitor administration increases radiosensitivity and suppresses tumor growth in non-small cell lung cancer

Authors
 Mi Youn Seol  ;  Seo Hee Choi  ;  Hong In Yoon 
Citation
 JOURNAL OF RADIATION RESEARCH, Vol.63(4) : 591-601, 2022-07 
Journal Title
JOURNAL OF RADIATION RESEARCH
ISSN
 0449-3060 
Issue Date
2022-07
MeSH
Carcinoma, Non-Small-Cell Lung* / drug therapy ; Carcinoma, Non-Small-Cell Lung* / radiotherapy ; Cell Line, Tumor ; Humans ; Lung Neoplasms* / drug therapy ; Lung Neoplasms* / genetics ; Lung Neoplasms* / radiotherapy ; Phosphatidylinositol 3-Kinases / metabolism ; Phosphoinositide-3 Kinase Inhibitors ; Protein Isoforms ; Proto-Oncogene Proteins c-akt / metabolism ; Radiation Tolerance ; Tumor Microenvironment
Keywords
PI3K isoform ; non-small cell lung cancer (NSCLC) ; radiation ; radioresistance ; radiosensitivity
Abstract
Non-small cell lung cancer (NSCLC) is a malignant lung tumor with a dismal prognosis. The activation of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway is common in many tumor types including NSCLC, which results in radioresistance and changes in the tumor microenvironment. Although pan-PI3K inhibitors have been tested in clinical trials to overcome radioresistance, concerns regarding their excessive side effects led to the consideration of selective inhibition of PI3K isoforms. In this study, we assessed whether combining radiation with the administration of the PI3K isoform-selective inhibitors reduces radioresistance and tumor growth in NSCLC. Inhibition of the PI3K/AKT pathway enhanced radiosensitivity substantially, and PI3K-α inhibitor showed superior radiosensitizing effect similar to PI3K pan-inhibitor, both in vitro and in vivo. Additionally, a significant increase in DNA double-strand breaks (DSB) and a decrease in migration ability were observed. Our study revealed that combining radiation and the PI3K-α isoform improved radiosensitivity that resulted in a significant delay in tumor growth and improved survival rate.
Files in This Item:
T202203228.pdf Download
DOI
10.1093/jrr/rrac018
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Yoon, Hong In(윤홍인) ORCID logo https://orcid.org/0000-0002-2106-6856
Choi, Seo Hee(최서희) ORCID logo https://orcid.org/0000-0002-4083-6414
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/191694
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