title: RNA interference targeting human FAK and EGFR suppresses human non-small-cell lung cancer xenograft growth in nude mice.
abstract: Transfection of plasmid vectors coexpressing short hairpin RNA (shRNA) for focal adhesion kinase (FAK) and epidermal growth factor receptor (EGFR) significantly inhibited protein level of FAK and EGFR. Knockdown of FAK and EGFR expression significantly inhibited cell proliferation and induced cell apoptosis of A549 lung cancer cells in vitro. In A549 subcutaneous xenograft model, mice treated for 3 weeks with plasmid that coexpresses FAK and EGFR shRNA had significantly smaller tumors than those in control mice (P < 0.01). FAK and EGFR dual silencing also significantly decreased microvessel density, tumor cell proliferation and increased the level of apoptosis in tumor cells. Moreover, administration with plasmid that coexpresses FAK and EGFR shRNA significantly inhibited the A549 experimental lung metastases. Collectively, our data suggest that the dual inhibition of FAK and EGFR by using plasmid vector-based RNA interference might be a novel therapeutic approach to the treatment of human NSCLC.
authors: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors: C
authors: C
authors: Li
authors: X
authors: X
authors: Zhang
authors: L
authors: L
authors: Cheng
authors: L
authors: L
authors: Dai
authors: F
authors: F
authors: Xu
authors: J
authors: J
authors: Zhang
authors: H
authors: H
authors: Tian
authors: X
authors: X
authors: Chen
authors: G
authors: G
authors: Shi
authors: Y
authors: Y
authors: Li
authors: T
authors: T
authors: Du
authors: S
authors: S
authors: Zhang
authors: Y
authors: Y
authors: Wei
authors: H
authors: H
authors: Deng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; C512478:EGFR protein, human; D066246:ErbB Receptors; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human