Nelfinavir induces radiation sensitization in pituitary adenoma cells

Cancer Biol Ther. 2011 Oct 1;12(7):657-63. doi: 10.4161/cbt.12.7.17172. Epub 2011 Oct 1.


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 days, 17 days with nelfinavir treatment, 27 days with radiation 6 Gy, and 41 days with nelfinavir plus radiation (one-way ANOVA p < 0.001). Decreased phospho-S6 on Western 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / drug therapy*
  • Adenoma / metabolism
  • Adenoma / pathology
  • Adenoma / radiotherapy*
  • Animals
  • Annexin A5 / metabolism
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Caspase 3 / metabolism
  • Cell Cycle / drug effects
  • Cell Cycle / radiation effects
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Nelfinavir / pharmacology*
  • Neoplasms, Experimental
  • Phosphatidylinositol 3-Kinases / metabolism
  • Pituitary Neoplasms / drug therapy*
  • Pituitary Neoplasms / metabolism
  • Pituitary Neoplasms / pathology
  • Pituitary Neoplasms / radiotherapy*
  • Prolactin / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Radiation-Sensitizing Agents / pharmacology*
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism
  • Xenograft Model Antitumor Assays


  • Annexin A5
  • Radiation-Sensitizing Agents
  • Prolactin
  • mTOR protein, mouse
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Caspase 3
  • Nelfinavir