The role of akt activation in the response to chemotherapy in pancreatic cancer

Colin M. Parsons, Diego Muilenburg, Tawnya L. Bowles, Subbulakshmi Virudachalam, Richard J Bold

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25 Scopus citations

Abstract

The PI3K/Akt signaling pathway is constitutively activated in some pancreatic cancers; when activated, it inhibits chemotherapy-mediated apoptosis. We examined whether Akt activity correlates with apoptotic resistance to chemotherapy in pancreatic cancer. Materials and Methods: A panel of human pancreatic cancer cells was evaluated for basal Akt activity as well as response to three chemotherapies. Chemotherapy-induced cell death was evaluated following either up- or down-regulation of Akt activity. Evaluation of phosphorylation of p21Cip/Waf1, a downstream target of Akt, was also evaluated. Results: There was a broad distribution among pancreatic cancer cell lines by Akt activity, as well as sensitivity to the three chemotherapeutic agents with no apparent correlation. Phosphorylation of p21Cip/Waf1, but not change in total levels, correlated with the chemosensitizing effect of Akt inhibition to paclitaxel. Conclusions: Basal Akt activity does not appear to be a useful predictor for selection of pancreatic cancers in targeting Akt to broadly induce chemosensitivity.

Original languageEnglish (US)
Pages (from-to)3279-3289
Number of pages11
JournalAnticancer Research
Volume30
Issue number9
StatePublished - Sep 2010

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Keywords

  • Akt
  • Apoptosis
  • Pancreatic cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Parsons, C. M., Muilenburg, D., Bowles, T. L., Virudachalam, S., & Bold, R. J. (2010). The role of akt activation in the response to chemotherapy in pancreatic cancer. Anticancer Research, 30(9), 3279-3289.