Radiation-inducible silencing of uPA and uPAR in vitro and in vivo in meningioma

  • Authors:
    • Venkateswara Rao Gogineni
    • Arun Kumar Nalla
    • Reshu Gupta
    • Bharathi Gorantla
    • Meena Gujrati
    • Dzung H. Dinh
    • Jasti S. Rao
  • View Affiliations

  • Published online on: April 1, 2010     https://doi.org/10.3892/ijo_00000557
  • Pages: 809-816
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Abstract

Stereospecific radiation treatment offers a distinct opportunity for temporal and spatial regulation of gene expression at tumor sites by means of inducible promoters. To this end, a plasmid, pCArG-U2, was constructed by incorporating nine CArG elements (in tandem) of EGR1 gene upstream to uPA and uPAR siRNA oligonucleotides in a pCi-neo vector. Radiation-induced siRNA expression was detected in a meningioma cell line (IOMM-Lee). Immunoblotting and RT-PCR analyses confirmed downregulation of uPA and uPAR. A similar effect was observed in transfected cells followed by H2O2 treatment. Moreover, pre-treatment of transfected cells with N-acetyl L-cysteine blocked the silencing of uPA and uPAR, which further confirmed the oxidative damage-mediated downregulation. Cell proliferation assays and Western blot analysis for apoptotic molecules confirmed cell death in a radiation-inducible fashion. Migration and matrigel invasion assays also revealed a marked decrease in migration and invasion. Immunocytochemistry showed a marked decrease in uPA and uPAR levels in transfected and irradiated cells. H&E staining revealed a decrease in the pre-established tumor volume among the animals treated with pCArG-U2 and radiation. Immunohistochemistry of the brain sections established with intracranial tumors also revealed a marked decrease in uPA and uPAR in a radiation-inducible fashion. Taken together, our data suggest pCArG-U2 as a suitable candidate for radiation-inducible gene therapy.

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April 2010
Volume 36 Issue 4

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

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Spandidos Publications style
Rao Gogineni V, Kumar Nalla A, Gupta R, Gorantla B, Gujrati M, Dinh DH and Rao JS: Radiation-inducible silencing of uPA and uPAR in vitro and in vivo in meningioma. Int J Oncol 36: 809-816, 2010
APA
Rao Gogineni, V., Kumar Nalla, A., Gupta, R., Gorantla, B., Gujrati, M., Dinh, D.H., & Rao, J.S. (2010). Radiation-inducible silencing of uPA and uPAR in vitro and in vivo in meningioma. International Journal of Oncology, 36, 809-816. https://doi.org/10.3892/ijo_00000557
MLA
Rao Gogineni, V., Kumar Nalla, A., Gupta, R., Gorantla, B., Gujrati, M., Dinh, D. H., Rao, J. S."Radiation-inducible silencing of uPA and uPAR in vitro and in vivo in meningioma". International Journal of Oncology 36.4 (2010): 809-816.
Chicago
Rao Gogineni, V., Kumar Nalla, A., Gupta, R., Gorantla, B., Gujrati, M., Dinh, D. H., Rao, J. S."Radiation-inducible silencing of uPA and uPAR in vitro and in vivo in meningioma". International Journal of Oncology 36, no. 4 (2010): 809-816. https://doi.org/10.3892/ijo_00000557