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International Journal of Oncology
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Article

Inhibitory effect of carbonyl reductase 1 on ovarian cancer growth via tumor necrosis factor receptor signaling

  • Authors:
    • Rie Miura
    • Yoshihito Yokoyama
    • Tatsuhiko Shigeto
    • Masayuki Futagami
    • Hideki Mizunuma
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan
  • Pages: 2173-2180
    |
    Published online on: October 13, 2015
       https://doi.org/10.3892/ijo.2015.3205
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Abstract

We investigated the mechanisms of the inhibitory effect of carbonyl reductase 1 (CR1) on ovarian cancer growth mediated by the activation of the tumor necrotic factor receptor (TNFR) pathway. OVCAR-3 and TOV21G cells overexpressing CR1 were constructed by transfecting them with CR1 cDNA by lipofection. CR1-overexpressing and control OVCAR-3 and TOV21G cells were injected subcutaneously into nude mice and the tumor growth was compared between the two groups for 3-4 weeks. The expression of TNFR1 and TNFR2 in tumors was examined immunohistochemically at the end of the experiment. Expression levels of caspase-8 and -3 activated by TNFR1, c-Jun activated by TNFR2, and NF-κB activated by both TNFR1 and TNFR2 were determined using immunohistochemistry and western blot analysis. Tumor growth was significantly suppressed in mice injected with CR1-overexpressing cells. Tumor volume in the CR1 induction group decreased temporarily until 2 weeks. Tumor cell membranes in both CR1 induction and control groups were positive for TNFR1 expression; however, total protein levels did not differ between the two groups. TNFR-2 expression was comparatively weak in both groups. The expression of NF-κB and c-Jun was weaker in the CR1 induction group than in control. In contrast, caspase-8 and -3 expression was higher in the CR1 induction group. Furthermore, the number of apoptotic cells was significantly greater in tumors that appeared after injections of both types of CR1-overexpressing cells than in those of control cancer cells. These results suggest that CR1 induces apoptosis by activating the caspase pathway via binding to TNFR1.
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Copy and paste a formatted citation
Spandidos Publications style
Miura R, Yokoyama Y, Shigeto T, Futagami M and Mizunuma H: Inhibitory effect of carbonyl reductase 1 on ovarian cancer growth via tumor necrosis factor receptor signaling. Int J Oncol 47: 2173-2180, 2015.
APA
Miura, R., Yokoyama, Y., Shigeto, T., Futagami, M., & Mizunuma, H. (2015). Inhibitory effect of carbonyl reductase 1 on ovarian cancer growth via tumor necrosis factor receptor signaling. International Journal of Oncology, 47, 2173-2180. https://doi.org/10.3892/ijo.2015.3205
MLA
Miura, R., Yokoyama, Y., Shigeto, T., Futagami, M., Mizunuma, H."Inhibitory effect of carbonyl reductase 1 on ovarian cancer growth via tumor necrosis factor receptor signaling". International Journal of Oncology 47.6 (2015): 2173-2180.
Chicago
Miura, R., Yokoyama, Y., Shigeto, T., Futagami, M., Mizunuma, H."Inhibitory effect of carbonyl reductase 1 on ovarian cancer growth via tumor necrosis factor receptor signaling". International Journal of Oncology 47, no. 6 (2015): 2173-2180. https://doi.org/10.3892/ijo.2015.3205
Copy and paste a formatted citation
x
Spandidos Publications style
Miura R, Yokoyama Y, Shigeto T, Futagami M and Mizunuma H: Inhibitory effect of carbonyl reductase 1 on ovarian cancer growth via tumor necrosis factor receptor signaling. Int J Oncol 47: 2173-2180, 2015.
APA
Miura, R., Yokoyama, Y., Shigeto, T., Futagami, M., & Mizunuma, H. (2015). Inhibitory effect of carbonyl reductase 1 on ovarian cancer growth via tumor necrosis factor receptor signaling. International Journal of Oncology, 47, 2173-2180. https://doi.org/10.3892/ijo.2015.3205
MLA
Miura, R., Yokoyama, Y., Shigeto, T., Futagami, M., Mizunuma, H."Inhibitory effect of carbonyl reductase 1 on ovarian cancer growth via tumor necrosis factor receptor signaling". International Journal of Oncology 47.6 (2015): 2173-2180.
Chicago
Miura, R., Yokoyama, Y., Shigeto, T., Futagami, M., Mizunuma, H."Inhibitory effect of carbonyl reductase 1 on ovarian cancer growth via tumor necrosis factor receptor signaling". International Journal of Oncology 47, no. 6 (2015): 2173-2180. https://doi.org/10.3892/ijo.2015.3205
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