Sufasalazine unveils a contact-independent HSV-TK/ganciclovir gene therapy bystander effect in malignant gliomas

  • Authors:
    • Pierre A. Robe
    • Minh-Tuan Nguyen-Khac
    • Frederic Lambert
    • Chantal Lechanteur
    • Olivier Jolois
    • Patricia Ernst-Gengoux
    • Bernard Rogister
    • Vincent Bours
  • View Affiliations

  • Published online on: January 1, 2007     https://doi.org/10.3892/ijo.30.1.283
  • Pages: 283-290
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Abstract

The efficacy of HSV-TK/ganciclovir-based gene therapy on malignant gliomas largely relies on the amplitude of the bystander effect. In these experiments, the anti-inflammatory drug Sulfasalazine increased the HSV-TK/ganciclovir bystander effect in C6, 9L and LN18 cells but not in U87 glioma cells. Using bi-compartmental culture devices and conditioned medium transfer experiments, we showed that in C6, 9L and LN18 cells but not in U87 cells, Sulfasalazine also unveiled a new, contact-independent mechanism of HSV-TK/ganciclovir bystander effect. Upon treatment with ganciclovir, human LN18-TK but not U87-TK cells synthetized and released TNF-α in the culture medium. Sulfasalazine sensitized glioma cells to the toxic effect of TNF-α and enhanced its secretion in LN18-TK cells in response to GCV treatment. The caspase-8 inhibitor Z-IETD-FMK and a blocking antibody to TNF-α both inhibited the contact-independent bystander effect in LN18 cells. Taken together, these results suggest that TNF-α mediates the contact-independent bystander effect in LN18 cells. The treatment with GCV and/or Sulfasalazine of tumor xenografts consisting of a mix of 98% C6 and 2% C6-TK cells shows that Sulfasalazine is also a potent adjunct to the in vivo treatment of gliomas.

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January 2007
Volume 30 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Robe PA, Nguyen-Khac M, Lambert F, Lechanteur C, Jolois O, Ernst-Gengoux P, Rogister B and Bours V: Sufasalazine unveils a contact-independent HSV-TK/ganciclovir gene therapy bystander effect in malignant gliomas. Int J Oncol 30: 283-290, 2007
APA
Robe, P.A., Nguyen-Khac, M., Lambert, F., Lechanteur, C., Jolois, O., Ernst-Gengoux, P. ... Bours, V. (2007). Sufasalazine unveils a contact-independent HSV-TK/ganciclovir gene therapy bystander effect in malignant gliomas. International Journal of Oncology, 30, 283-290. https://doi.org/10.3892/ijo.30.1.283
MLA
Robe, P. A., Nguyen-Khac, M., Lambert, F., Lechanteur, C., Jolois, O., Ernst-Gengoux, P., Rogister, B., Bours, V."Sufasalazine unveils a contact-independent HSV-TK/ganciclovir gene therapy bystander effect in malignant gliomas". International Journal of Oncology 30.1 (2007): 283-290.
Chicago
Robe, P. A., Nguyen-Khac, M., Lambert, F., Lechanteur, C., Jolois, O., Ernst-Gengoux, P., Rogister, B., Bours, V."Sufasalazine unveils a contact-independent HSV-TK/ganciclovir gene therapy bystander effect in malignant gliomas". International Journal of Oncology 30, no. 1 (2007): 283-290. https://doi.org/10.3892/ijo.30.1.283