Role of p53, Bax, p21, and DNA-PKcs in radiation sensitivity of HCT-116 cells and xenografts

Sergio Huerta, Xiaohuan Gao, Sean Dineen, Payal Kapur, Debrabata Saha, Jeffrey Meyer

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Background: Molecular factors that dictate tumor response to ionizing radiation in rectal cancer are not well described. Methods: We investigated the contribution of p53, p21, Bax, and DNA-PKcs in response to ionizing radiation in an isogeneic colorectal cancer system in vitro and in vivo. Results: HCT-116 DNA-PKcs-/- cells and xenografts were radiosensitive compared with wild-type (WT) HCT-116 cells. HCT-116 p53-/- cells and tumor xenografts displayed a radioresistant phenotype. Separately, p21 or Bax deficiency was associated with a radiosensitive phenotype in vitro and in vivo. In vivo, Bax deficiency led to increased tumor necrosis and decreased microvessel density. In vitro, HCT-116 Bax-/- cells had decreased levels of vascular endothelial growth factor. HCT-116 WT cells had a more radioresistant phenotype after pancaspase inhibition, but pancaspase inhibition did not alter radiosensitivity in HCT-116 Bax-/- cells subjected to ionizing radiation. There was no difference in cell growth in HCT-116 WT cells subjected to transient apoptosis-inducing factor (AIF) inhibition; however, HCT-116 Bax-/- cells treated with AIF siRNA followed by ionizing radiation had a significant survival advantage compared with control-treated cells, implicating AIF in the radiosensitivity of Bax-/- cells. Conclusion: These data might be used along with other markers to predict response to radiation in patients with rectal cancer.

Original languageEnglish (US)
Pages (from-to)143-151
Number of pages9
JournalSurgery (United States)
Volume154
Issue number2
DOIs
StatePublished - Aug 1 2013

ASJC Scopus subject areas

  • Surgery

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