Inhibition of bacillus Calmette-Guérin-induced nitric oxide in bladder tumor cells may improve BCG treatment

  • Authors:
    • Valeria Alvarez
    • Catalina Lodillinsky
    • Sol Umerez
    • Eduardo Sandes
    • Ana María Eiján
  • View Affiliations

  • Published online on: October 1, 2005     https://doi.org/10.3892/ijmm.16.4.565
  • Pages: 565-571
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Abstract

Bacillus Calmette-Guérin (BCG) is considered to be one of the most effective treatments for superficial and in situ bladder cancer. However, either failure to respond initially or relapse within the first 5 years of treatment has been observed in some patients. As nitric oxide (NO) has been detected in the bladder of BCG-treated patients, we analyzed the role of endogenous NO generated after BCG treatments on human (T24) and murine (MB49 and MBT2) bladder tumor cells in the viability of tumor and immune cells, both in vitro and in vivo. In vitro inhibition of cancer cells after BCG treatment was evaluated by cell titer assay. NO production was determined as nitrite by Griess reagent. The death of immunocytes was evaluated by 51Cr release. Tumor histology with hematoxylin and eosin and Masson's trichrome staining was performed. BCG induced a direct inhibition of tumor cell growth in vitro, independently of NO levels. Besides, BCG-mediated NO production by tumor cells induced the death of spleen and peritoneal cells in syngeneic mice. The in vivo inhibition of NO synthase (NOS) activity by NG-nitro-L-arginine methyl ester in combination with BCG, improved tumor regression by generating a healing tissue. The increase of NO generated after BCG administration may induce the death of immunocytes. The in vivo inhibition of NO ameliorated immunotherapy with BCG by additional tumor growth inhibition. Our results suggested the possibility that the final outcome of patients with bladder tumors may improve by modulating NOS activity concomitantly with BCG therapy.

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October 2005
Volume 16 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Alvarez V, Lodillinsky C, Umerez S, Sandes E and Eiján AM: Inhibition of bacillus Calmette-Guérin-induced nitric oxide in bladder tumor cells may improve BCG treatment. Int J Mol Med 16: 565-571, 2005.
APA
Alvarez, V., Lodillinsky, C., Umerez, S., Sandes, E., & Eiján, A.M. (2005). Inhibition of bacillus Calmette-Guérin-induced nitric oxide in bladder tumor cells may improve BCG treatment. International Journal of Molecular Medicine, 16, 565-571. https://doi.org/10.3892/ijmm.16.4.565
MLA
Alvarez, V., Lodillinsky, C., Umerez, S., Sandes, E., Eiján, A. M."Inhibition of bacillus Calmette-Guérin-induced nitric oxide in bladder tumor cells may improve BCG treatment". International Journal of Molecular Medicine 16.4 (2005): 565-571.
Chicago
Alvarez, V., Lodillinsky, C., Umerez, S., Sandes, E., Eiján, A. M."Inhibition of bacillus Calmette-Guérin-induced nitric oxide in bladder tumor cells may improve BCG treatment". International Journal of Molecular Medicine 16, no. 4 (2005): 565-571. https://doi.org/10.3892/ijmm.16.4.565