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HPB (Oxford). 2011 Sep;13(9):597-604. doi: 10.1111/j.1477-2574.2011.00333.x. Epub 2011 Jun 7.

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

Author information

  • 1Division of Surgical Oncology, Department of Surgery, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390-8548, USA.

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.

PMID:
21843259
PMCID:
PMC3183443
DOI:
10.1111/j.1477-2574.2011.00333.x
[PubMed - indexed for MEDLINE]
Free PMC Article
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