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
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  • Published online on: August 24, 2012     https://doi.org/10.3892/or.2012.1992
  • Pages: 1693-1700
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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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November 2012
Volume 28 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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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