Silencing of the type 1 insulin-like growth factor receptor increases the sensitivity to apoptosis and inhibits invasion in human lung adenocarcinoma A549 cells.
The type 1 insulin-like growth factor receptor (IGF-1R), which is over-expressed or activated in many human cancers, including lung cancer, mediates cancer cell proliferation and metastasis. Several studies indicate that blocking IGF-1R expression can inhibit tumor cell proliferation and metastasis. In this study, inhibition of the endogenous IGF-1R by recombinant adenoviruses encoding short hairpin RNAs against IGF-1R was found to significantly suppress IGF-1R expression, arrest the cell cycle, enhance the apoptotic response, and inhibit proliferation, adhesion, invasion and migration in A549 cells. Moreover, silencing IGF-1R decreases the expression of invasive-related genes including matrix metalloproteinase-2 (MMP-2), MMP-9, and urokinase-plasminogen activator (u-PA), and the phosphorylation of Akt and ERK1/2. These results suggest that the silencing of IGF-1R has the potential to be an effective cancer gene therapy strategy for human lung cancer.
Ma
Zhiyuan
Z
Department of Cardiothoracic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.
Dong
Aiqiang
A
Kong
Minjian
M
Qian
Jianfang
J
D000230:Adenocarcinoma / Q000378:metabolism*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002448:Cell Adhesion; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D034622:RNA Interference; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D017526:Receptor, IGF Type 1; D014568:Urokinase-Type Plasminogen Activator; D053148:Caspase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9