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 language | English (US) |
|---|---|
| Pages (from-to) | 3279-3289 |
| Number of pages | 11 |
| Journal | Anticancer Research |
| Volume | 30 |
| Issue number | 9 |
| State | Published - Sep 2010 |
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Keywords
- Akt
- Apoptosis
- Pancreatic cancer
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
The role of akt activation in the response to chemotherapy in pancreatic cancer. / Parsons, Colin M.; Muilenburg, Diego; Bowles, Tawnya L.; Virudachalam, Subbulakshmi; Bold, Richard J.
In: Anticancer Research, Vol. 30, No. 9, 09.2010, p. 3279-3289.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The role of akt activation in the response to chemotherapy in pancreatic cancer
AU - Parsons, Colin M.
AU - Muilenburg, Diego
AU - Bowles, Tawnya L.
AU - Virudachalam, Subbulakshmi
AU - Bold, Richard J
PY - 2010/9
Y1 - 2010/9
N2 - 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.
AB - 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.
KW - Akt
KW - Apoptosis
KW - Pancreatic cancer
UR - http://www.scopus.com/inward/record.url?scp=77958578733&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77958578733&partnerID=8YFLogxK
M3 - Article
VL - 30
SP - 3279
EP - 3289
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 9
ER -