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Article

Zoledronic acid inhibits the pentose phosphate pathway through attenuating the Ras‑TAp73‑G6PD axis in bladder cancer cells

  • Authors:
    • Xiaolin Wang
    • Guang Wu
    • Guangxin Cao
    • Lei Yang
    • Haifei Xu
    • Jian Huang
    • Jianquan Hou
  • View Affiliations / Copyright

    Affiliations: Department of Urology, First Affiliated Hospital, Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Urology, First People's Hospital of Wujiang, Suzhou, Jiangsu 215200, P.R. China, Department of Urology, Nantong Tumor Hospital, Nantong, Jiangsu 226361, P.R. China, Department of Medical Oncology, Nantong Tumor Hospital, Nantong, Jiangsu 226361, P.R. China
  • Pages: 4620-4625
    |
    Published online on: June 24, 2015
       https://doi.org/10.3892/mmr.2015.3995
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Abstract

Zoledronic acid (ZA) is the current standard of care for the therapy of patients with bone metastasis or osteoporosis. ZA inhibits the prenylation of small guanosine‑5'-triphosphate (GTP)‑binding proteins, such as Ras, and thus inhibit Ras signaling. The present study demonstrated that ZA inhibited cell proliferation and the pentose phosphate pathway (PPP) in bladder cancer cells. In addition, the expression of glucose‑6‑phosphate dehydrogenase (G6PD, the rate‑limiting enzyme of the PPP) was found to be inhibited by ZA. Furthermore, the stability of TAp73, which activates the expression G6PD was decreased in zoledronic acid treated cells. Decreased levels of Ras‑GTP and phosphorylated‑extracellular signal-regulated kinase 1/2 were also observed following treatment with ZA. This may be due to the fact that activated Ras was reported to stabilize TAp73 inducing its accumulation. The inhibition of Ras activity by PT inhibitor II also significantly reduced the levels of TAp73 and G6PD and the PPP flux. Moreover, knockdown of TAp73, attenuated the PPP flux and eliminated the affection of ZA on the PPP flux. In conclusion, it was proposed that ZA can inhibit stability of TAp73 and attenuate the PPP via blocking Ras signaling in bladder cancer cells.
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Copy and paste a formatted citation
Spandidos Publications style
Wang X, Wu G, Cao G, Yang L, Xu H, Huang J and Hou J: Zoledronic acid inhibits the pentose phosphate pathway through attenuating the Ras‑TAp73‑G6PD axis in bladder cancer cells. Mol Med Rep 12: 4620-4625, 2015.
APA
Wang, X., Wu, G., Cao, G., Yang, L., Xu, H., Huang, J., & Hou, J. (2015). Zoledronic acid inhibits the pentose phosphate pathway through attenuating the Ras‑TAp73‑G6PD axis in bladder cancer cells. Molecular Medicine Reports, 12, 4620-4625. https://doi.org/10.3892/mmr.2015.3995
MLA
Wang, X., Wu, G., Cao, G., Yang, L., Xu, H., Huang, J., Hou, J."Zoledronic acid inhibits the pentose phosphate pathway through attenuating the Ras‑TAp73‑G6PD axis in bladder cancer cells". Molecular Medicine Reports 12.3 (2015): 4620-4625.
Chicago
Wang, X., Wu, G., Cao, G., Yang, L., Xu, H., Huang, J., Hou, J."Zoledronic acid inhibits the pentose phosphate pathway through attenuating the Ras‑TAp73‑G6PD axis in bladder cancer cells". Molecular Medicine Reports 12, no. 3 (2015): 4620-4625. https://doi.org/10.3892/mmr.2015.3995
Copy and paste a formatted citation
x
Spandidos Publications style
Wang X, Wu G, Cao G, Yang L, Xu H, Huang J and Hou J: Zoledronic acid inhibits the pentose phosphate pathway through attenuating the Ras‑TAp73‑G6PD axis in bladder cancer cells. Mol Med Rep 12: 4620-4625, 2015.
APA
Wang, X., Wu, G., Cao, G., Yang, L., Xu, H., Huang, J., & Hou, J. (2015). Zoledronic acid inhibits the pentose phosphate pathway through attenuating the Ras‑TAp73‑G6PD axis in bladder cancer cells. Molecular Medicine Reports, 12, 4620-4625. https://doi.org/10.3892/mmr.2015.3995
MLA
Wang, X., Wu, G., Cao, G., Yang, L., Xu, H., Huang, J., Hou, J."Zoledronic acid inhibits the pentose phosphate pathway through attenuating the Ras‑TAp73‑G6PD axis in bladder cancer cells". Molecular Medicine Reports 12.3 (2015): 4620-4625.
Chicago
Wang, X., Wu, G., Cao, G., Yang, L., Xu, H., Huang, J., Hou, J."Zoledronic acid inhibits the pentose phosphate pathway through attenuating the Ras‑TAp73‑G6PD axis in bladder cancer cells". Molecular Medicine Reports 12, no. 3 (2015): 4620-4625. https://doi.org/10.3892/mmr.2015.3995
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