Anticancer effects of gemcitabine are enhanced by co-administered iRGD peptide in murine pancreatic cancer models that overexpressed neuropilin-1.
Anticancer effects of gemcitabine are enhanced by co-administered iRGD peptide in murine pancreatic cancer models that overexpressed neuropilin-1.
复制标题
DOI：
10.1038/bjc.2014.49
复制
发表时间：
2014-03-18
影响因子：
8.8
通讯作者：
Ohkohchi, N.
中科院分区：
文献类型：
--
作者：
Akashi, Y.;Oda, T.;Ohara, Y.;Miyamoto, R.;Kurokawa, T.;Hashimoto, S.;Enomoto, T.;Yamada, K.;Satake, M.;Ohkohchi, N.
受损的药物转运是降低抗癌剂对胰腺癌的功效的重要因素。在这里，我们报告了一种新的联合化疗使用吉西他滨（GEM）和内化的RGD（iRGD）肽，增强肿瘤特异性药物渗透结合神经纤毛蛋白-1（NRP 1）受体。总共5个胰腺癌小鼠模型（2个基于细胞系的异种移植物（CX）和3个肿瘤移植物（TG））单独使用GEM（100 mg kg−1，q3 d × 4）或GEM + iRGD肽（8 μmol kg−1）治疗。通过免疫组织化学（IHC）评价异种移植物和48例临床癌症标本中的NRP 1表达。我们确定了一个子集的胰腺癌模型，显示NRP 1过表达的iRGD共同管理敏感。在CX中，与GEM单一疗法相比，GEM加iRGD肽治疗导致肿瘤显著减少，但在TG中不显著。iRGD的潜在靶点被表征为显示NRP 1过表达（IHC-2+/3+）的病例，这些病例占临床标本的45.8%。内化的RGD肽增强了胰腺癌模型中共同施用的药物的作用，然而其功效仅在采用细胞系的那些中是可感知的。因此，临床应用需要仔细考虑。
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. 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). 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. 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.
登录
查看更多内容
影响因子：
5.7
作者：
Hidalgo M;Bruckheimer E;Rajeshkumar NV;Garrido-Laguna I;De Oliveira E;Rubio-Viqueira B;Strawn S;Wick MJ;Martell J;Sidransky D
通讯作者：
Sidransky D
DOI：
10.1083/jcb.200910104
发表时间：
2010-03-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ruoslahti E;Bhatia SN;Sailor MJ
通讯作者：
Sailor MJ
影响因子：
50.3
作者：
Sugahara KN;Teesalu T;Karmali PP;Kotamraju VR;Agemy L;Girard OM;Hanahan D;Mattrey RF;Ruoslahti E
通讯作者：
Ruoslahti E
影响因子：
11.5
作者：
Fukahi, K;Fukasawa, M;Korc, M
通讯作者：
Korc, M
影响因子：
45.3
作者：
Burris, HA;Moore, MJ;VanHoff, DD
通讯作者：
VanHoff, DD