SU11248 (Sunitinib) Sensitizes Pancreatic Cancer to the Cytotoxic Effects of Ionizing Radiation

Kyle C. Cuneo, Ling Geng, Allie Fu, Darren Orton, Dennis E. Hallahan, Anuradha Bapsi Chakravarthy

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Purpose: SU11248 (sunitinib) is a small-molecule tyrosine kinase inhibitor which targets VEGFR and PDGFR isoforms. In the present study, the effects of SU11248 and ionizing radiation on pancreatic cancer were studied. Methods and Materials: For in vitro studies human pancreatic adenocarcinoma cells lines were treated with 1 μM SU11248 1 h before irradiation. Western blot analysis was used to determine the effect of SU11248 on radiation-induced signal transduction. To determine if SU11248 sensitized pancreatic cancer to the cytotoxic effects of ionizing radiation, a clonogenic survival assay was performed using 0-6 Gy. For in vivo assays, CAPAN-1 cells were injected into the hind limb of nude mice for tumor volume and proliferation studies. Results: SU11248 attenuated radiation-induced phosphorylation of Akt and ERK at 0, 5, 15, and 30 min. Furthermore, SU11248 significantly reduced clonogenic survival after treatment with radiation (p < 0.05). In vivo studies revealed that SU11248 and radiation delayed tumor growth by 6 and 10 days, respectively, whereas combined treatment delayed tumor growth by 30 days. Combined treatment with SU11248 and radiation further attenuated Brdu incorporation by 75% (p = 0.001) compared to control. Conclusions: SU11248 (sunitinib) sensitized pancreatic cancer to the cytotoxic effects of radiation. This compound is promising for future clinical trials with chemoradiation in pancreatic cancer.

Original languageEnglish
Pages (from-to)873-879
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume71
Issue number3
DOIs
StatePublished - Jul 1 2008
Externally publishedYes

Keywords

  • PDGFR
  • Pancreatic cancer
  • Radiosensitizer
  • SU11248
  • Sunitinib
  • VEGFR

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