AKT inhibition by triciribine alone or as combination therapy for growth control of gastroenteropancreatic neuroendocrine tumors

  • Authors:
    • Christoph R. Gloesenkamp
    • Bianca Nitzsche
    • Matthias Ocker
    • Pietro Di Fazio
    • Karl Quint
    • Björn Hoffmann
    • Hans Scherübl
    • Michael Höpfner
  • View Affiliations

  • Published online on: November 7, 2011     https://doi.org/10.3892/ijo.2011.1256
  • Pages: 876-888
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Abstract

Up-regulation of phosphatidylinositol-3-kinase (PI3K)-AKT signaling facilitates tumor cell growth and inhibits cell demise. The AKT-pathway also plays an important role in cytostatic therapy resistance and response to hypoxia and angiogenesis. Using real-time cell proliferation assay we examined the potency of triciribine in three distinct neuroendocrine gastrointestinal tumor cell lines. Also we investigated triciribine's induction of apoptosis and effects on a broad range of cancer-associated gene products. Furthermore, we characterized the role of PTEN as a possible predictor of sensitivity to triciribine in GEP-NETs. We also looked for additive anti-neoplastic effects of triciribine when combined with conventional cytostatic drugs or other targeted drugs, affecting different molecules of the PI3K-AKT-pathway and we assessed the potency of triciribine to inhibit tumor growth in vivo, by using the chick chorioallantoic membrane assay. Treatment of insulinoma (CM) or gut neuroendocrine tumor cells (STC-1) with triciribine significantly reduced tumor cell growth by 59% and 65%, respectively. By contrast, the highly expressing PTEN carcinoid cell line BON did not respond, even at higher doses. Combinations of triciribine with classic cytostatic drugs as well as drugs targeting other molecules of the PI3K-AKT-pathway led to synergistic anti-proliferative effects. Additional in vivo-evaluations confirmed the anti-neoplastic potency of triciribine. Thus, our data show that inhibition the AKT-pathway potently reduces the growth of GEP-NET cells alone or in combination therapies. AKT inhibition may provide a rationale for future evaluations.

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March 2012
Volume 40 Issue 3

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Spandidos Publications style
Gloesenkamp CR, Nitzsche B, Ocker M, Di Fazio P, Quint K, Hoffmann B, Scherübl H and Höpfner M: AKT inhibition by triciribine alone or as combination therapy for growth control of gastroenteropancreatic neuroendocrine tumors. Int J Oncol 40: 876-888, 2012
APA
Gloesenkamp, C.R., Nitzsche, B., Ocker, M., Di Fazio, P., Quint, K., Hoffmann, B. ... Höpfner, M. (2012). AKT inhibition by triciribine alone or as combination therapy for growth control of gastroenteropancreatic neuroendocrine tumors. International Journal of Oncology, 40, 876-888. https://doi.org/10.3892/ijo.2011.1256
MLA
Gloesenkamp, C. R., Nitzsche, B., Ocker, M., Di Fazio, P., Quint, K., Hoffmann, B., Scherübl, H., Höpfner, M."AKT inhibition by triciribine alone or as combination therapy for growth control of gastroenteropancreatic neuroendocrine tumors". International Journal of Oncology 40.3 (2012): 876-888.
Chicago
Gloesenkamp, C. R., Nitzsche, B., Ocker, M., Di Fazio, P., Quint, K., Hoffmann, B., Scherübl, H., Höpfner, M."AKT inhibition by triciribine alone or as combination therapy for growth control of gastroenteropancreatic neuroendocrine tumors". International Journal of Oncology 40, no. 3 (2012): 876-888. https://doi.org/10.3892/ijo.2011.1256