title: Effects of insulin-like growth factor 1 receptor and its inhibitor AG1024 on the progress of lung cancer.
abstract: The type 1 insulin-like growth factor receptor (IGF-1R) and its downstream signaling components have been increasingly recognized to drive the development of malignancies, including non-small cell lung cancer (NSCLC). This study aimed to investigate the effects of IGF-1R and its inhibitor, AG1024, on the progression of lung cancer. Tissue microarray and immunohistochemistry were employed to detect the expressions of IGF-1 and IGF-1R in NSCLC tissues (n=198). Western blotting was used to determine the expressions of IGF-1 and phosphorylated IGF-1R (p-IGF-1R) in A549 human lung carcinoma cells, and MTT assay to measure cell proliferation. Additionally, the expressions of IGF-1, p-IGF-1R and IGF-1R in a mouse model of lung cancer were detected by Western blotting and real-time fluorescence quantitative polymerase chain reaction (FQ-PCR), respectively. The results showed that IGF-1 and IGF-1R were overexpressed in NSCLC tissues. The expression levels of IGF-1 and p-IGF-1R were significantly increased in A549 cells treated with IGF-1 as compared to those treated with IGF-1+AG1024 or untreated cells. In the presence of IGF-1, the proliferation of A549 cells was significantly increased. The progression of lung cancer in mice treated with IGF-1 was significantly increased as compared to the group treated with IGF-1+AG1024 or the control group, with the same trend mirrored in IGF-1/p-IGF-1R/IGF-1R at the protein and/or mRNA levels. It was concluded that IGF-1 and IGF inhibitor AG1024 promotes lung cancer progression.
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Wei
authors.affiliation: Department of Thoracic Surgery, Huazhong University of Science and Technology, Wuhan, 430030, China.|Department of Intensive Care Unit, Wuhan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China.
authors.forename: He-Xiao
authors.initials: HX
authors.lastname: Tang
authors.affiliation: Department of Thoracic Surgery, Huazhong University of Science and Technology, Wuhan, 430030, China. liaotjxw@126.com.
authors.forename: Yong-de
authors.initials: YD
authors.lastname: Liao
authors.affiliation: Department of Thoracic Surgery, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Sheng-Ling
authors.initials: SL
authors.lastname: Fu
authors.affiliation: Department of Thoracic Surgery, Huazhong University of Science and Technology, Wuhan, 430030, China.|Department of Thoracic Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, China.
authors.forename: Li-Qiang
authors.initials: LQ
authors.lastname: Xu
authors.affiliation: Department of Thoracic Surgery, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, Huazhong University of Science and Technology, Wuhan, 430030, China.|Department of Respiratory Medicine, the Central Hospital of Yichang, Yichang, 443000, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Huazhong University of Science and Technology, Wuhan, 430030, China.|Department of Thoracic Surgery, Zhejiang Hospital, Hangzhou, 310000, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Ju
authors.affiliation: Department of Thoracic Surgery, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Zhao-Guo
authors.initials: ZG
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Liang-Kun
authors.initials: LK
authors.lastname: You
authors.affiliation: Department of Intensive Care Unit, Wuhan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D020032:Tyrphostins / Q000494:pharmacology*
chemical_list: D020032:Tyrphostins; C447031:tyrphostin AG 1024; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1
keywords: AG1024; insulin-like growth factor-1 receptor; lung cancer; mouse lung adenocarcinoma model