Effects of insulin-like growth factor 1 receptor and its inhibitor AG1024 on the progress of lung cancer.
10.1007/s11596-015-1515-1
- Author:
Yan-hong WEI
1
;
He-xiao TANG
2
;
Yong-de LIAO
3
;
Sheng-ling FU
4
;
Li-qiang XU
4
;
Guang CHEN
4
;
Chao ZHANG
4
;
Sheng JU
4
;
Zhao-guo LIU
4
;
Liang-kun YOU
4
;
Li YU
5
;
Sheng ZHOU
6
Author Information
1. Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. 394384280@qq.com.
2. Department of Thoracic Surgery, Huazhong University of Science and Technology, Wuhan, 430030, China. thx1245@sina.com.
3. Department of Thoracic Surgery, Huazhong University of Science and Technology, Wuhan, 430030, China. liaotjxw@126.com.
4. Department of Thoracic Surgery, Huazhong University of Science and Technology, Wuhan, 430030, China.
5. Department of Intensive Care Unit, Wuhan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China.
6. Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
- Publication Type:Journal Article
- Keywords:
AG1024;
insulin-like growth factor-1 receptor;
lung cancer;
mouse lung adenocarcinoma model
- MeSH:
Adult;
Aged;
Animals;
Carcinoma, Non-Small-Cell Lung;
metabolism;
pathology;
Cell Proliferation;
Disease Models, Animal;
Disease Progression;
Female;
Humans;
Insulin-Like Growth Factor I;
metabolism;
Lung Neoplasms;
metabolism;
pathology;
Male;
Mice;
Middle Aged;
Receptor, IGF Type 1;
antagonists & inhibitors;
physiology;
Tyrphostins;
pharmacology
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2015;35(6):834-841
- CountryChina
- Language:English
-
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.
