title: The cyclooxygenase-2 inhibitor NS-398 inhibits proliferation and induces             apoptosis in human osteosarcoma cells via downregulation of the survivin pathway.
abstract: Cyclooxygenase-2 (COX-2) is frequently overexpressed in human malignancies             and plays a crucial role in tumorigenesis and cancer progression. The present             study aimed to investigate the expression and clinical significance of COX-2 and             survivin (SUV) in human osteosarcomas (OS), and explore the effects and molecular             mechanisms of a selective COX-2 inhibitor NS-398 and SUV on tumor proliferation             and apoptosis. Fifty cases of human OS and osteochondromas (OC) were collected.             The expression of COX-2 and SUV was assessed using immunohistochemical assays             in biopsy samples. MG-63 human OS cells were treated with different concentrations             of NS-398, used to investigate their effects on cell proliferation and apoptosis.             The recombinant small hairpin RNA adenovirus vector rAd5-SUV was constructed,             and the effects and molecular mechanisms of knockdown of SUV on proliferation             and apoptosis were evaluated in MG-63 cells. A subcutaneous xenograft tumor model             was established, validating the effects of rAd5-SUV on tumor growth in vivo. Based             on the results, the expression of COX-2 and SUV in OS showed a higher strong reactivity             rate compared with OC (73.3 vs. 25.0%, P=0.001; 63.3 vs. 30.0%, P=0.02), but it             did not correlate with the clinicopathological characteristics of OS. NS-398 inhibited             proliferation, induced apoptosis and decreased the mRNA expression of COX-2 and             SUV in MG-63 cells. Furthermore, adenovirus-mediated knockdown of SUV inhibited             proliferation, induced apoptosis, reduced the expression of proliferating cell             nuclear antigen (PCNA), increased the expression of caspase-3 (CAS-3) and slowed             the growth of xenograft tumors in MG-63 cells. Taken together, the expression             of COX-2 and SUV is closely correlated with human OS, and inhibition of COX-2             or knockdown of SUV suppresses tumor proliferation and induces apoptosis, suggesting             that COX-2 may be involved in OS cell proliferation and apoptosis through SUV-mediated             regulation of PCNA and CAS-3 expression, and provides a potential therapeutic             strategy for the treatment of cancer.
authors.affiliation: Department of Orthopedics, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, PR China.
authors.forename: Da-Peng
authors.initials: DP
authors.lastname: Duan
authors.forename: Xiao-Qian
authors.initials: XQ
authors.lastname: Dang
authors.forename: Kun-Zheng
authors.initials: KZ
authors.lastname: Wang
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Wu-Lin
authors.initials: WL
authors.lastname: You
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015536:Down-Regulation; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009578:Nitrobenzenes / Q000494:pharmacology*; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D034622:RNA Interference; D034741:RNA, Small Interfering; D013449:Sulfonamides / Q000494:pharmacology*; D000077022:Survivin; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C107489:BIRC5 protein, human; D052246:Cyclooxygenase 2 Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D009578:Nitrobenzenes; D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering; D013449:Sulfonamides; D000077022:Survivin; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D053148:Caspase 3