Cuneo KC et al. – SU11248 (sunitinib) sensitized pancreatic cancer to cytotoxic effects of radiation and has potential for future clinical trials with chemoradiation in pancreatic cancer Methods
Study of the effects of SU11248 and ionizing radiation on pancreatic cancer
In vitro studies: human pancreatic adenocarcinoma cells lines treated with 1 microM SU11248 1 h before irradiation
Western blot analysis for effect of SU11248 on radiation-induced signal transduction
Clonogenic survival assay using 0–6 Gy to determine if SU11248 sensitized pancreatic cancer to cytotoxic effects of ionizing radiation
In vivo assays: CAPAN-1 cells 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
SU11248 significantly reduced clonogenic survival after treatment with radiation
In vivo studies showed that SU11248 and radiation delayed tumor growth by 6 and 10 days, respectively; combined treatment delayed tumor growth by 30 days
Combined treatment with SU11248 and radiation further attenuated Brdu incorporation by 75% compared with controls
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