Open AccessIGF-1R Inhibition Suppresses Cell Proliferation and Increases Radiosensitivity in Nasopharyngeal Carcinoma Cells
Author(s) -
Zhe Wang,
Guangyan Liu,
Mao Jiwei,
Min Xie,
Ming Zhao,
Xuefen Guo,
Shangdong Liang,
Heming Li,
Xuefeng Liu,
Ruo–Yu Wang
Publication year - 2019
Publication title -
mediators of inflammation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.37
H-Index - 97
eISSN - 1466-1861
pISSN - 0962-9351
DOI - 10.1155/2019/5497467
Subject(s) - radioresistance , nasopharyngeal carcinoma , radiosensitivity , cancer research , cell growth , cell cycle , protein kinase b , apoptosis , biology , mapk/erk pathway , cell culture , growth inhibition , cell cycle checkpoint , phosphorylation , medicine , radiation therapy , microbiology and biotechnology , biochemistry , genetics
Although ionizing radiation (IR) has provided considerable improvements in nasopharyngeal carcinoma (NPC) treatment, radioresistance is still a major threat for some subsets of patients. The insulin-like growth factor-1 receptor (IGF-1R) signaling pathway is tightly regulated and plays critical roles in mediating cell proliferation, growth, and survival. Thus, IGF-1R may be a potential therapeutic target for patients with different malignancies. However, its mechanism in NPC is not fully investigated. Linsitinib is an oral small molecule and is a tyrosine kinase inhibitor (TKI) of IGF-1R, which has been known for antitumor effects used widely. Here, we evaluated the proliferation and radiosensitivity of NPC cell lines (CNE-2 and SUNE-1) after linsitinib treatment. We found that linsitinib suppresses IGF-1-induced cell proliferation through inhibiting Akt and ERK phosphorylation. Moreover, linsitinib further boosted IR-induced DNA damage, G2-M cell cycle delay, and apoptosis in NPC cells. Finally, linsitinib reversed radioresistant NPC cells by decreasing the phosphorylation of IGF-1R. Our data indicated that the combination of linsitinib and IR and targeting IGF-1R by linsitinib could be a promising therapeutic strategy for NPC.