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Article

mTOR inhibition reduces growth and adhesion of hepatocellular carcinoma cells in vitro

  • Authors:
    • Tobias Engl
    • Jochen Rutz
    • Sebastian Maxeiner
    • Eva Juengel
    • Frederik Roos
    • Wael Khoder
    • Wolf O. Bechstein
    • Karen Nelson
    • Igor Tsaur
    • Axel Haferkamp
    • Roman A. Blaheta
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Goethe‑University, D‑60590 Frankfurt am Main, Germany, Department of Vascular and Endovascular Surgery, Goethe‑University, D‑60590 Frankfurt am Main, Germany
  • Pages: 7064-7071
    |
    Published online on: August 31, 2017
       https://doi.org/10.3892/mmr.2017.7401
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Abstract

Mechanistic target of rapamycin (mTOR) signaling is typically increased in hepatocellular carcinoma (HCC). A panel of HCC cell lines (HepG2, Hep3B and HuH6) was exposed to various concentrations of the mTOR inhibitors, everolimus and temsirolimus, in order to investigate their effects on cell growth, clonal formation, cell cycle progression, and adhesion and chemotactic migration using MTT and clonal cell growth assays, fluorometric detection of cell cycle phases and a Boyden chamber assay. In addition, integrin α and β adhesion receptors were analyzed by flow cytometry and blocking studies using function blocking monoclonal antibodies were conducted to explore functional relevance. The results demonstrated that everolimus and temsirolimus significantly suppressed HCC cell growth and clonal formation, at 0.1 or 1 nM (depending on the cell line). In addition, the number of cells in G0/G1 phase was increased in response to drug treatment, whereas the number of G2/M phase cells was decreased. Drug treatment also considerably suppressed HCC cell adhesion to immobilized collagen. Integrin profiling revealed strong expression of integrin α1, α2, α6 and β1 subtypes; and integrin α1 was upregulated in response to mTOR inhibition. Suppression of integrin α1 did not affect cell growth; however, it did significantly decrease adhesion and chemotaxis, with the influence on adhesion being greater than that on motility. Due to a positive association between integrin α1 expression and the extent of adhesion, whereby reduced receptor expression was correlated to decreased cell adhesion, it may be hypothesized that the adhesion‑blocking effects of mTOR inhibitors are not associated with mechanical contact inhibition of the α1 receptor but with integrin α1‑dependent suppression of oncogenic signaling, thus preventing tumor cell‑matrix interaction.
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Copy and paste a formatted citation
Spandidos Publications style
Engl T, Rutz J, Maxeiner S, Juengel E, Roos F, Khoder W, Bechstein WO, Nelson K, Tsaur I, Haferkamp A, Haferkamp A, et al: mTOR inhibition reduces growth and adhesion of hepatocellular carcinoma cells in vitro. Mol Med Rep 16: 7064-7071, 2017.
APA
Engl, T., Rutz, J., Maxeiner, S., Juengel, E., Roos, F., Khoder, W. ... Blaheta, R.A. (2017). mTOR inhibition reduces growth and adhesion of hepatocellular carcinoma cells in vitro. Molecular Medicine Reports, 16, 7064-7071. https://doi.org/10.3892/mmr.2017.7401
MLA
Engl, T., Rutz, J., Maxeiner, S., Juengel, E., Roos, F., Khoder, W., Bechstein, W. O., Nelson, K., Tsaur, I., Haferkamp, A., Blaheta, R. A."mTOR inhibition reduces growth and adhesion of hepatocellular carcinoma cells in vitro". Molecular Medicine Reports 16.5 (2017): 7064-7071.
Chicago
Engl, T., Rutz, J., Maxeiner, S., Juengel, E., Roos, F., Khoder, W., Bechstein, W. O., Nelson, K., Tsaur, I., Haferkamp, A., Blaheta, R. A."mTOR inhibition reduces growth and adhesion of hepatocellular carcinoma cells in vitro". Molecular Medicine Reports 16, no. 5 (2017): 7064-7071. https://doi.org/10.3892/mmr.2017.7401
Copy and paste a formatted citation
x
Spandidos Publications style
Engl T, Rutz J, Maxeiner S, Juengel E, Roos F, Khoder W, Bechstein WO, Nelson K, Tsaur I, Haferkamp A, Haferkamp A, et al: mTOR inhibition reduces growth and adhesion of hepatocellular carcinoma cells in vitro. Mol Med Rep 16: 7064-7071, 2017.
APA
Engl, T., Rutz, J., Maxeiner, S., Juengel, E., Roos, F., Khoder, W. ... Blaheta, R.A. (2017). mTOR inhibition reduces growth and adhesion of hepatocellular carcinoma cells in vitro. Molecular Medicine Reports, 16, 7064-7071. https://doi.org/10.3892/mmr.2017.7401
MLA
Engl, T., Rutz, J., Maxeiner, S., Juengel, E., Roos, F., Khoder, W., Bechstein, W. O., Nelson, K., Tsaur, I., Haferkamp, A., Blaheta, R. A."mTOR inhibition reduces growth and adhesion of hepatocellular carcinoma cells in vitro". Molecular Medicine Reports 16.5 (2017): 7064-7071.
Chicago
Engl, T., Rutz, J., Maxeiner, S., Juengel, E., Roos, F., Khoder, W., Bechstein, W. O., Nelson, K., Tsaur, I., Haferkamp, A., Blaheta, R. A."mTOR inhibition reduces growth and adhesion of hepatocellular carcinoma cells in vitro". Molecular Medicine Reports 16, no. 5 (2017): 7064-7071. https://doi.org/10.3892/mmr.2017.7401
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