Nelfinavir induces radiation sensitization in pituitary adenoma cells

Jing Zeng, Alfred P. See, Khaled Aziz, Saravanan Thiyagarajan, Tarek Salih, Rajendra P. Gajula, Michael Armour, Jillian Phallen, Stephanie Terezakis, Lawrence Kleinberg, Kristen Redmond, Russell K. Hales, Roberto Salvatori, Alfredo Quinones-Hinojosa, Phuoc T. Tran, Michael Lim

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Pituitary adenomas with local invasion and high secretory activity remain a therapeutic challenge. The HIV protease inhibitor nelfinavir is a radiosensitizer in multiple tumor models. We tested nelfinavir as a radiosensitizer in pituitary adenoma cells in vitro and in vivo. We examined the effect of nelfinavir with radiation on in vitro cell viability, clonogenic survival, apoptosis, prolactin secretion, cell cycle distribution and the PI3K-AKT-mTOR pathway. We evaluated tumor growth delay and confirmed nelfinavir's effect on the PI3K-AKT-mTOR pathway in a hind-flank model. Nelfinavir sensitized pituitary adenoma cells to ionizing radiation as shown by viability assays and clonogenic assay with an enhancement ratio of 1.2 (p < 0.05). There is increased apoptotic cell death, as determined by annexin-V expression and cleaved caspase-3 levels. Nelfinavir does not affect prolactin secretion or cell cycle distribution. In vivo, untreated tumors reached 4-fold volume in 12 d, 17 d with nelfinavir treatment, 27 d with radiation 6 Gy, and 41 d with nelfinavir plus radiation (one-way ANOVA p < 0.001). Decreased phospho-S6 on protein gel blotting in vitro and immunohistochemistry in vivo demonstrated nelfinavir inhibition of the PI3K-AKT-mTOR pathway. Our data suggests a promising combination therapy with nelfinavir plus radiation in pituitary adenomas, which should be investigated in clinical studies.

Original languageEnglish (US)
Pages (from-to)657-663
Number of pages7
JournalCancer Biology and Therapy
Volume12
Issue number7
DOIs
StatePublished - Oct 1 2011
Externally publishedYes

Fingerprint

Nelfinavir
Pituitary Neoplasms
Radiation
Phosphatidylinositol 3-Kinases
Prolactin
Cell Cycle
HIV Protease Inhibitors
S 6
Radiation Dosage
Neoplasms
Annexin A5
Ionizing Radiation
Caspase 3
Cell Survival
Analysis of Variance
Cell Death
Therapeutics
Gels
Immunohistochemistry

Keywords

  • Nelfinavir
  • PI3K-AKT-mTOR
  • Pituitary adenomas
  • Radiosensitizer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology

Cite this

Zeng, J., See, A. P., Aziz, K., Thiyagarajan, S., Salih, T., Gajula, R. P., ... Lim, M. (2011). Nelfinavir induces radiation sensitization in pituitary adenoma cells. Cancer Biology and Therapy, 12(7), 657-663. https://doi.org/10.4161/cbt.12.7.17172

Nelfinavir induces radiation sensitization in pituitary adenoma cells. / Zeng, Jing; See, Alfred P.; Aziz, Khaled; Thiyagarajan, Saravanan; Salih, Tarek; Gajula, Rajendra P.; Armour, Michael; Phallen, Jillian; Terezakis, Stephanie; Kleinberg, Lawrence; Redmond, Kristen; Hales, Russell K.; Salvatori, Roberto; Quinones-Hinojosa, Alfredo; Tran, Phuoc T.; Lim, Michael.

In: Cancer Biology and Therapy, Vol. 12, No. 7, 01.10.2011, p. 657-663.

Research output: Contribution to journalArticle

Zeng, J, See, AP, Aziz, K, Thiyagarajan, S, Salih, T, Gajula, RP, Armour, M, Phallen, J, Terezakis, S, Kleinberg, L, Redmond, K, Hales, RK, Salvatori, R, Quinones-Hinojosa, A, Tran, PT & Lim, M 2011, 'Nelfinavir induces radiation sensitization in pituitary adenoma cells', Cancer Biology and Therapy, vol. 12, no. 7, pp. 657-663. https://doi.org/10.4161/cbt.12.7.17172
Zeng J, See AP, Aziz K, Thiyagarajan S, Salih T, Gajula RP et al. Nelfinavir induces radiation sensitization in pituitary adenoma cells. Cancer Biology and Therapy. 2011 Oct 1;12(7):657-663. https://doi.org/10.4161/cbt.12.7.17172
Zeng, Jing ; See, Alfred P. ; Aziz, Khaled ; Thiyagarajan, Saravanan ; Salih, Tarek ; Gajula, Rajendra P. ; Armour, Michael ; Phallen, Jillian ; Terezakis, Stephanie ; Kleinberg, Lawrence ; Redmond, Kristen ; Hales, Russell K. ; Salvatori, Roberto ; Quinones-Hinojosa, Alfredo ; Tran, Phuoc T. ; Lim, Michael. / Nelfinavir induces radiation sensitization in pituitary adenoma cells. In: Cancer Biology and Therapy. 2011 ; Vol. 12, No. 7. pp. 657-663.
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