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Celecoxib synergizes human pancreatic ductal adenocarcinoma cells to sorafenib-induced growth inhibition.

Författare

Summary, in English

BACKGROUND:

Pancreatic ductal adenocarcinoma is frequently associated with aberrant activation of the Ras/Raf/MAPK pathway and cyclooxygenase-2 (COX-2) overexpression. This study evaluated the potential for combining the multikinase inhibitor sorafenib and the specific COX-2 inhibitor celecoxib as therapy in pancreatic ductal adenocarcinoma cells.



METHODS:

BxPC-3, MIAPaCa-2, PANC-1 and AsPC-1 pancreatic adenocarcinoma cells were exposed to sorafenib and celecoxib combined treatment in vitro. Cell viability and various growth promoting and survival signaling pathways were monitored by MTT, flow cytometry and Western blotting.



RESULTS:

Combined treatment with sorafenib and celecoxib synergistically inhibited pancreatic adenocarcinoma cell proliferation. This regimen produced combination index (CI) values between 0.67 and 0.92 for the various cell lines, indicating significant synergistic interactions between sorafenib and celecoxib, which also markedly inhibited the migratory capacity. The growth inhibition was associated with an accumulation of cells in the G(0)/G(1) phase of the cell cycle and induction of apoptosis. These changes were accompanied by a significant reduction of p21(WAF1/Cip1) levels, where celecoxib sensitized the cells to sorafenib-mediated p21(WAF1/Cip1) suppression.



CONCLUSION:

These results suggest that combined treatment with sorafenib and celecoxib synergistically induce growth inhibition and apoptosis in pancreatic adenocarcinoma cells through a process involving p21(WAF1/Cip1) suppression

Avdelning/ar

  • Kirurgi, Lund
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publiceringsår

2012

Språk

Engelska

Sidor

219-226

Publikation/Tidskrift/Serie

Pancreatology

Volym

12

Issue

3

Dokumenttyp

Artikel i tidskrift

Förlag

Karger

Ämne

  • Surgery

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1424-3903