AKT inhibition is associated with chemosensitisation in the pancreatic cancer cell line MIA-PaCa-2

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Updated: Sep 23, 2026

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
09:19

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo

Published on: February 6, 2015

B N Fahy1, M Schlieman, S Virudachalam

  • 1Department of Surgical Oncology, University of California Davis Cancer Center, Sacramento, CA 95817, USA.

British Journal of Cancer
|July 17, 2003
PubMed

Insights

Inhibiting AKT in pancreatic cancer cells lowers anti-apoptotic BCL-2 and increases pro-apoptotic BAX, sensitizing tumors to chemotherapy by affecting NF-kappaB signaling.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Activation of the serine/threonine kinase AKT is frequently observed in pancreatic cancer.
  • AKT activation confers resistance to apoptosis, a key challenge in pancreatic cancer treatment.

Purpose of the Study:

  • To investigate the role of AKT signaling in regulating the BCL-2 gene family.
  • To determine how AKT influences NF-kappaB activity and its downstream transcriptional targets.
  • To evaluate the impact of inhibiting AKT on chemotherapy-induced apoptosis in pancreatic cancer cells.

Main Methods:

  • Inhibition of phosphatidylinositol-3 kinase (PI3K) or AKT.
  • Assessment of BCL-2 and BAX protein levels.
  • Measurement of NF-kappaB transcription factor activity.
  • Evaluation of apoptosis induction by chemotherapy.

Main Results:

  • Inhibition of PI3K or AKT decreased anti-apoptotic BCL-2 protein and increased pro-apoptotic BAX protein.
  • AKT inhibition reduced NF-kappaB activity, impacting the transcriptional regulation of BCL-2.
  • While basal apoptosis was minimally affected, chemotherapy-induced apoptosis was significantly enhanced.

Conclusions:

  • AKT activation in pancreatic cancer promotes apoptosis resistance, potentially via transcriptional induction of BCL-2 family proteins.
  • Targeting the AKT/NF-kappaB pathway can sensitize pancreatic cancer cells to chemotherapy.
  • Modulating this pathway offers a potential strategy to improve pancreatic cancer treatment outcomes.

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