title: Depression of focal adhesion kinase induces apoptosis in rat osteosarcoma OSR-6 cells in a caspase-dependent pathway.
abstract: Focal adhesion kinase (FAK), a nonreceptor tyrosine kinase protein, acts as an early modulator of integrin signaling cascade, regulating basic cellular functions. In transformed cells, unopposed FAK signaling has been considered to promote tumor growth, progression, and metastasis. The aim of this study was to assess the role of FAK in rat osteosarcoma OSR-6 cells. OSR-6 cells were transfected with PGPU6/GFP/shNC (shNC), and PGPU6/GFP/FAK-2434 (shRNA-2434), separately. Expression of FAK was detected by Real-time PCR and Western blots. MTT assay was used to examine changes in cell proliferation. Cell apoptosis was analyzed by flow cytometry. The expression of caspase-3,-7,-9 was measured by Western blots. The expression of FAK in OSR-6 cells significantly decreased in shRNA-2434 group in contrast to the control group (P < 0.01). Cell proliferation was inhibited by shRNA-2434 and shRNA-2434+ cisplatin, and the effects were clearly enhanced when cells were treated with anticancer agents. The level of cell apoptosis in shRNA-2434 and shRNA-2434+ cisplatin group was higher than that in the control group (P < 0.01). The current data support evidence that down-regulation of FAK could induce rat osteosarcoma cells (OSR-6) apoptosis through the caspase-dependent cell death pathway. Inhibition of the kinases may be important for therapies designed to enhance the apoptosis in osteosarcoma.
authors.affiliation: Department of Emergency Surgery, First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Harbin, 150001, Heilongjiang, China, shuo_yang0@163.com.
authors.forename: Shuo
authors.initials: S
authors.lastname: Yang
authors.forename: Liming
authors.initials: L
authors.lastname: Wang
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Kong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics*; D006801:Humans; D012516:Osteosarcoma / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D034741:RNA, Small Interfering; D051416:Focal Adhesion Protein-Tyrosine Kinases; D053148:Caspase 3; D020169:Caspases; D002945:Cisplatin