Ribozyme to TGF-β1 mRNA abrogates immunosuppressive effects of human colorectal adenocarcinoma HRT-18 cells in vitro and in vivo

  • Authors:
    • Wolfgang Daniel Schmitt
    • Antje Siegert
    • Sandra Stephanie Lach
    • Stephan Fuhrmann
    • Anke Kondla
    • Per Sonne Holm
    • Steffen Hauptmann
  • View Affiliations

  • Published online on: October 1, 2009     https://doi.org/10.3892/ijo_00000405
  • Pages: 901-908
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Abstract

Transforming growth factor-β1 (TGF-β1) is overexpressed in a variety of malignant epithelial tumors and was suggested to be a marker of colorectal cancer. Moreover, there is growing evidence that TGF-β1 contributes to tumor progression by regulating tumor cell proliferation and differentiation, inducing a favorable tumor microenvironment, promoting migration and invasion, and suppressing macrophage cytotoxicity. Therefore, we stably transfected an anti-TGF-β1 hammerhead ribozyme into the human colorectal adenocarcinoma cell line HRT-18. Expression of this ribozyme resulted in significant inhibition of TGF-β1 expression on mRNA and protein level. This was associated with an enhanced tumor cell differentiation and a reduced tumor growth in vivo. The capability of tumor cells to suppress ROI production of co-cultivated human macrophages was abrogated in transfectants. Taken together, inhibition of TGF-β1 in colorectal carcinoma cells might be an interesting therapeutic tool leading to reduced tumor cell growth and increased macrophage cytotoxicity. Thus, a gene-therapeutic approach using anti-TGF-β1 ribozyme in combination with established anti-tumor agents is of great promise.

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October 2009
Volume 35 Issue 4

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

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Spandidos Publications style
Schmitt WD, Siegert A, Lach SS, Fuhrmann S, Kondla A, Holm PS and Hauptmann S: Ribozyme to TGF-β1 mRNA abrogates immunosuppressive effects of human colorectal adenocarcinoma HRT-18 cells in vitro and in vivo. Int J Oncol 35: 901-908, 2009
APA
Schmitt, W.D., Siegert, A., Lach, S.S., Fuhrmann, S., Kondla, A., Holm, P.S., & Hauptmann, S. (2009). Ribozyme to TGF-β1 mRNA abrogates immunosuppressive effects of human colorectal adenocarcinoma HRT-18 cells in vitro and in vivo. International Journal of Oncology, 35, 901-908. https://doi.org/10.3892/ijo_00000405
MLA
Schmitt, W. D., Siegert, A., Lach, S. S., Fuhrmann, S., Kondla, A., Holm, P. S., Hauptmann, S."Ribozyme to TGF-β1 mRNA abrogates immunosuppressive effects of human colorectal adenocarcinoma HRT-18 cells in vitro and in vivo". International Journal of Oncology 35.4 (2009): 901-908.
Chicago
Schmitt, W. D., Siegert, A., Lach, S. S., Fuhrmann, S., Kondla, A., Holm, P. S., Hauptmann, S."Ribozyme to TGF-β1 mRNA abrogates immunosuppressive effects of human colorectal adenocarcinoma HRT-18 cells in vitro and in vivo". International Journal of Oncology 35, no. 4 (2009): 901-908. https://doi.org/10.3892/ijo_00000405