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: Yan-Hong Wei, He-Xiao Tang, Yong-de Liao, Sheng-Ling Fu, Li-Qiang Xu, Guang Chen, Chao Zhang, Sheng Ju, Zhao-Guo Liu, Liang-Kun You, Li Yu, Sheng Zhou
• Journal: Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban (J Huazhong Univ Sci Technolog Med Sci) Vol. 35 Issue 6 Pg. 834-841 (Dec 2015) ISSN: 1993-1352 [Electronic] China
• PMID: 26670433 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tyrphostins
• tyrphostin AG 1024
• Insulin-Like Growth Factor I
• Receptor, IGF Type 1

Topics

• 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)