Antitumour activity of sunitinib in combination with gemcitabine in experimental pancreatic cancer

Niranjan Awasthi, Margaret A. Schwarz, Roderich E. Schwarz

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Background: Gemcitabine (Gem) has limited clinical benefits in pancreatic ductal adenocarcinoma (PDAC). Sunitinib (Su) is a novel, multi-target receptor tyrosine kinase inhibitor that has antitumour activities. This study tested the benefits of combined gemcitabine and sunitinib in PDAC. Methods: Cell viability and protein expression were evaluated by WST-1 assay and Western blotting. Tumour growth and survival experiments were performed in murine xenografts. Results: In PDAC cells, Gem, Su and Su + Gem, respectively, caused 28%, 22% and 48% inhibition in proliferation at 100 nM. In endothelial cells, Gem, Su and Su + Gem, respectively, caused 49%, 32% and 72% inhibition in proliferation. In fibroblasts, Gem, Su and Su + Gem, respectively, caused 65%, 14% and 79% inhibition in proliferation. Su increased apoptosis, as evidenced by the cleavage of caspase-3 and PARP-1 proteins. Net tumour growth compared with controls in the Gem, Su and Su + Gem groups was 57%, 6% and 1%, respectively. Intratumoral proliferative activity was reduced by 33%, 82% and 75% in the Gem, Su and Su + Gem groups, respectively, compared with controls. Median survival in the control, Su, Gem and Su + Gem groups was 16, 21, 24 and 30 days, respectively (P= 0.007). Conclusions: These findings support a combination approach using multi-target antiangiogenic agents such as sunitinib with standard gemcitabine therapy in the treatment of PDAC.

Original languageEnglish (US)
Pages (from-to)597-604
Number of pages8
JournalHPB
Volume13
Issue number9
DOIs
StatePublished - Sep 2011
Externally publishedYes

Keywords

  • combination therapy
  • gemcitabine
  • pancreatic cancer
  • sunitinib

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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