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.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Akashi Y,Oda T,Ohara Y,Miyamoto R,Kurokawa T,Hashimoto S,Enomoto T,Yamada K,Satake M,Ohkohchi Ndoi
10.1038/bjc.2014.49subject
Has Abstractpub_date
2014-03-18 00:00:00pages
1481-7issue
6eissn
0007-0920issn
1532-1827pii
bjc201449journal_volume
110pub_type
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journal_title：British journal of cancer
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doi：10.1038/bjc.1993.91
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pub_type： 临床试验,杂志文章
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pub_type： 临床试验,杂志文章,多中心研究
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