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Article

The cyclooxygenase-2 inhibitor NS-398 inhibits proliferation and induces apoptosis in human osteosarcoma cells via downregulation of the survivin pathway

  • Authors:
    • Da-Peng Duan
    • Xiao-Qian Dang
    • Kun-Zheng Wang
    • Yong-Ping Wang
    • Hui Zhang
    • Wu-Lin You
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedics, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, P.R. China, Department of Orthopaedics, Sixth People's Hospital of Shanghai JiaoTong University, Shanghai 200233, P.R. China, Department of Orthopaedics, Gansu Provincial People's Hospital, Lanzhou 730000, Gansu Province, P.R. China
  • Pages: 1693-1700
    |
    Published online on: August 24, 2012
       https://doi.org/10.3892/or.2012.1992
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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.
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Copy and paste a formatted citation
Spandidos Publications style
Duan D, Dang X, Wang K, Wang Y, Zhang H and You W: The cyclooxygenase-2 inhibitor NS-398 inhibits proliferation and induces apoptosis in human osteosarcoma cells via downregulation of the survivin pathway. Oncol Rep 28: 1693-1700, 2012.
APA
Duan, D., Dang, X., Wang, K., Wang, Y., Zhang, H., & You, W. (2012). The cyclooxygenase-2 inhibitor NS-398 inhibits proliferation and induces apoptosis in human osteosarcoma cells via downregulation of the survivin pathway. Oncology Reports, 28, 1693-1700. https://doi.org/10.3892/or.2012.1992
MLA
Duan, D., Dang, X., Wang, K., Wang, Y., Zhang, H., You, W."The cyclooxygenase-2 inhibitor NS-398 inhibits proliferation and induces apoptosis in human osteosarcoma cells via downregulation of the survivin pathway". Oncology Reports 28.5 (2012): 1693-1700.
Chicago
Duan, D., Dang, X., Wang, K., Wang, Y., Zhang, H., You, W."The cyclooxygenase-2 inhibitor NS-398 inhibits proliferation and induces apoptosis in human osteosarcoma cells via downregulation of the survivin pathway". Oncology Reports 28, no. 5 (2012): 1693-1700. https://doi.org/10.3892/or.2012.1992
Copy and paste a formatted citation
x
Spandidos Publications style
Duan D, Dang X, Wang K, Wang Y, Zhang H and You W: The cyclooxygenase-2 inhibitor NS-398 inhibits proliferation and induces apoptosis in human osteosarcoma cells via downregulation of the survivin pathway. Oncol Rep 28: 1693-1700, 2012.
APA
Duan, D., Dang, X., Wang, K., Wang, Y., Zhang, H., & You, W. (2012). The cyclooxygenase-2 inhibitor NS-398 inhibits proliferation and induces apoptosis in human osteosarcoma cells via downregulation of the survivin pathway. Oncology Reports, 28, 1693-1700. https://doi.org/10.3892/or.2012.1992
MLA
Duan, D., Dang, X., Wang, K., Wang, Y., Zhang, H., You, W."The cyclooxygenase-2 inhibitor NS-398 inhibits proliferation and induces apoptosis in human osteosarcoma cells via downregulation of the survivin pathway". Oncology Reports 28.5 (2012): 1693-1700.
Chicago
Duan, D., Dang, X., Wang, K., Wang, Y., Zhang, H., You, W."The cyclooxygenase-2 inhibitor NS-398 inhibits proliferation and induces apoptosis in human osteosarcoma cells via downregulation of the survivin pathway". Oncology Reports 28, no. 5 (2012): 1693-1700. https://doi.org/10.3892/or.2012.1992
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