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Article

Synergistic induction of apoptosis by mapatumumab and anthracyclines in human bladder cancer cells

  • Authors:
    • Syed Minhaj Uddin Ahmed
    • Xiuxian Wu
    • Xinghua Jin
    • Xia Zhang
    • Yoshikazu Togo
    • Toru Suzuki
    • Yongnan Li
    • Akihiro Kanematsu
    • Mikio Nojima
    • Shingo Yamamoto
    • Mikio Sugimoto
    • Yoshiyuki Kakehi
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Faculty of Medicine, Kagawa University, Kita-gun, Kagawa 761-0793, Japan, Department of Urology, Hyogo Medical College, Nishinomiya City, Hyogo 663-8501, Japan
  • Pages: 566-572
    |
    Published online on: December 5, 2014
       https://doi.org/10.3892/or.2014.3654
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Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in a variety of tumor cells by engaging the death receptors 4 (DR4) and 5 (DR5). We investigated the effect of chemotherapeutic drugs on DR4-mediated apoptosis in human bladder cancer cells, using a human monoclonal agonistic antibody specific for DR4, mapatumumab. Cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Synergy was assessed by isobolographic analysis. Treatment of human bladder cancer T24 cells with mapatumumab in combination with mitomycin C, vinblastine or gemcitabine did not overcome resistance to these agents. However, treatment with mapatumumab in combination with epirubicin (EPI) had a synergistic cytotoxic effect. Synergy was also obtained in KU7 and RT112 human bladder cancer cells. A synergistic effect was also observed with mapatumumab in combination with pirarubicin. The synergy obtained in cytotoxicity with mapatumumab and EPI was also achieved in apoptosis. EPI markedly increased DR4 expression in the bladder cancer cells at both the mRNA and protein levels. Furthermore, the combination-induced cytotoxicity was significantly suppressed by the DR4:Fc chimeric protein. The combination of EPI and mapatumumab significantly activated the caspase cascade, including caspase-8, -9 and -3, which are the downstream molecules of death receptors. These findings indicate that EPI sensitizes bladder cancer cells to DR4-mediated apoptosis through induction of DR4 and activation of caspases, suggesting that the combination therapy of EPI and mapatumumab may be effective for bladder cancer therapy.
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Copy and paste a formatted citation
Spandidos Publications style
Ahmed SU, Wu X, Jin X, Zhang X, Togo Y, Suzuki T, Li Y, Kanematsu A, Nojima M, Yamamoto S, Yamamoto S, et al: Synergistic induction of apoptosis by mapatumumab and anthracyclines in human bladder cancer cells. Oncol Rep 33: 566-572, 2015.
APA
Ahmed, S.U., Wu, X., Jin, X., Zhang, X., Togo, Y., Suzuki, T. ... Kakehi, Y. (2015). Synergistic induction of apoptosis by mapatumumab and anthracyclines in human bladder cancer cells. Oncology Reports, 33, 566-572. https://doi.org/10.3892/or.2014.3654
MLA
Ahmed, S. U., Wu, X., Jin, X., Zhang, X., Togo, Y., Suzuki, T., Li, Y., Kanematsu, A., Nojima, M., Yamamoto, S., Sugimoto, M., Kakehi, Y."Synergistic induction of apoptosis by mapatumumab and anthracyclines in human bladder cancer cells". Oncology Reports 33.2 (2015): 566-572.
Chicago
Ahmed, S. U., Wu, X., Jin, X., Zhang, X., Togo, Y., Suzuki, T., Li, Y., Kanematsu, A., Nojima, M., Yamamoto, S., Sugimoto, M., Kakehi, Y."Synergistic induction of apoptosis by mapatumumab and anthracyclines in human bladder cancer cells". Oncology Reports 33, no. 2 (2015): 566-572. https://doi.org/10.3892/or.2014.3654
Copy and paste a formatted citation
x
Spandidos Publications style
Ahmed SU, Wu X, Jin X, Zhang X, Togo Y, Suzuki T, Li Y, Kanematsu A, Nojima M, Yamamoto S, Yamamoto S, et al: Synergistic induction of apoptosis by mapatumumab and anthracyclines in human bladder cancer cells. Oncol Rep 33: 566-572, 2015.
APA
Ahmed, S.U., Wu, X., Jin, X., Zhang, X., Togo, Y., Suzuki, T. ... Kakehi, Y. (2015). Synergistic induction of apoptosis by mapatumumab and anthracyclines in human bladder cancer cells. Oncology Reports, 33, 566-572. https://doi.org/10.3892/or.2014.3654
MLA
Ahmed, S. U., Wu, X., Jin, X., Zhang, X., Togo, Y., Suzuki, T., Li, Y., Kanematsu, A., Nojima, M., Yamamoto, S., Sugimoto, M., Kakehi, Y."Synergistic induction of apoptosis by mapatumumab and anthracyclines in human bladder cancer cells". Oncology Reports 33.2 (2015): 566-572.
Chicago
Ahmed, S. U., Wu, X., Jin, X., Zhang, X., Togo, Y., Suzuki, T., Li, Y., Kanematsu, A., Nojima, M., Yamamoto, S., Sugimoto, M., Kakehi, Y."Synergistic induction of apoptosis by mapatumumab and anthracyclines in human bladder cancer cells". Oncology Reports 33, no. 2 (2015): 566-572. https://doi.org/10.3892/or.2014.3654
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