[HTML][HTML] Anticancer effects of gemcitabine are enhanced by co-administered iRGD peptide in murine pancreatic cancer models that overexpressed neuropilin-1
Y Akashi, T Oda, Y Ohara, R Miyamoto… - British journal of …, 2014 - nature.com
Y Akashi, T Oda, Y Ohara, R Miyamoto, T Kurokawa, S Hashimoto, T Enomoto, K Yamada…
British journal of cancer, 2014•nature.comBackground: Impaired drug transport is an important factor that reduces the efficacy of
anticancer agents against pancreatic cancer. Here, we report a novel combination
chemotherapy using gemcitabine (GEM) and internalised-RGD (iRGD) peptide, which
enhances tumour-specific drug penetration by binding neuropilin-1 (NRP1) receptor.
Methods: A total of five pancreatic cancer murine models (two cell line-based xenografts
(CXs) and three tumour grafts (TGs)) were treated with either GEM (100 mg kg− 1, q3d× 4) …
anticancer agents against pancreatic cancer. Here, we report a novel combination
chemotherapy using gemcitabine (GEM) and internalised-RGD (iRGD) peptide, which
enhances tumour-specific drug penetration by binding neuropilin-1 (NRP1) receptor.
Methods: A total of five pancreatic cancer murine models (two cell line-based xenografts
(CXs) and three tumour grafts (TGs)) were treated with either GEM (100 mg kg− 1, q3d× 4) …
Abstract
Background:
Impaired drug transport is an important factor that reduces the efficacy of anticancer agents against pancreatic cancer. Here, we report a novel combination chemotherapy using gemcitabine (GEM) and internalised-RGD (iRGD) peptide, which enhances tumour-specific drug penetration by binding neuropilin-1 (NRP1) receptor.
Methods:
A total of five pancreatic cancer murine models (two cell line-based xenografts (CXs) and three tumour grafts (TGs)) were treated with either GEM (100 mg kg− 1, q3d× 4) alone or GEM plus iRGD peptide (8 μmol kg− 1). Evaluation of NRP1 expression in xenografts and 48 clinical cancer specimens was performed by immunohistochemistry (IHC).
Results:
We identified a subset of pancreatic cancer models that showed NRP1 overexpression sensitive to iRGD co-administration. Treatment with GEM plus iRGD peptide resulted in a significant tumour reduction compared with GEM monotherapy in CXs, but not remarkable in TGs. Potential targets of iRGD were characterised as cases showing NRP1 overexpression (IHC-2+/3+), and these accounted for 45.8% of the clinical specimens.
Conclusions:
Internalised RGD peptide enhances the effects of co-administered drugs in pancreatic cancer models, its efficacy is however only appreciable in those employing cell lines. Therefore, the clinical application needs to be given careful consideration.
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