PMID- 22186885
OWN - NLM
STAT- MEDLINE
DCOM- 20120727
LR  - 20171116
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Linking)
VI  - 69
IP  - 4
DP  - 2012 Apr
TI  - CIP-13F, a novel aminopeptidase N (APN/CD13) inhibitor, inhibits Lewis lung 
      carcinoma growth and metastasis in mice.
PG  - 1029-38
LID - 10.1007/s00280-011-1799-1 [doi]
AB  - PURPOSE: Aminopeptidase N (APN/CD13) is highly expressed on the surface of cancer 
      cells and is thought to be involved in cancer growth and metastasis. The research 
      of APN/CD13 inhibitors is considered as a strategy of cancer treatment. We aimed 
      to evaluate the efficacy of CIP-13F, a novel APN/CD13 inhibitor, using a Lewis 
      lung carcinoma (LLC) implantation mouse model. METHODS: C57BL/6 mice were 
      subcutaneously inoculated with LLC cells in anterior flank. Then, 0, 50 and 100 
      mg/kg of CIP-13F were injected via vena caudalis. Bestatin was used as the 
      positive control. Administration of CIP-13F or bestatin was performed daily for 3 
      consecutive weeks. Mice were killed, and the tumors in anterior flank and 
      metastasis nodules in lungs were examined. The assays of immunohistochemical 
      staining, immunofluorescent flow cytometry and western blotting were performed to 
      estimate the expression of APN/CD13 in LLC cells. We carried out the experiments 
      of Annexin-V/PI staining, DNA fragmentation analysis and terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining to 
      determine apoptotic cells in LLC tissues. Using immunohistochemical staining with 
      CD34, the antiangiogenesis of CIP-13F was evaluated in LLC tissue sections. 
      RESULTS: CIP-13F treatment resulted in a significant delay of LLC growth in 
      anterior flank. Examination of lungs showed that the number of metastatic nodules 
      of LLC was also markedly decreased. The inhibitory effect of CIP-13F on LLC 
      growth was further evidenced by the induction of LLC apoptosis, showing the 
      increases in Annexin-V/PI staining cells, DNA fragmentation and TUNEL staining 
      cells. Molecular analyses of LLC tissues in CIP-13F-treated mice suggested that 
      the decrease in APN/CD13 expression by CIP-13F might account for its actions of 
      mechanism. Further, the inhibition of angiogenesis in LLC tissues was determined, 
      showing the decreases in microvessel density (MVD) and angiogenic factors 
      including vascular endothelial growth factor (VEGF), basic fibroblast growth 
      factor (bFGF) and transforming growth factor-alpha (TGF-alpha). CONCLUSION: Our 
      results showed that CIP-13F effectively inhibited LLC growth and pulmonary 
      metastasis in mice and suggested that CIP-13F is a potential drug for the 
      treatment for cancers with positive APN/CD13 expression.
FAU - Pei, Ke-Ling
AU  - Pei KL
AD  - Key Laboratory for Rare Disease of Shandong Province, Department of Pharmacology, 
      Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan 250062, 
      China.
FAU - Yuan, Yi
AU  - Yuan Y
FAU - Qin, San-Hai
AU  - Qin SH
FAU - Wang, Yan
AU  - Wang Y
FAU - Zhou, Ling
AU  - Zhou L
FAU - Zhang, Hou-Li
AU  - Zhang HL
FAU - Qu, Xian-Jun
AU  - Qu XJ
FAU - Cui, Shu-Xiang
AU  - Cui SX
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111221
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 
      (2-amino-N-(1-(2-(hydroxyamino)-2-oxoethyl)-2,6-dioxopiperidin-3-yl)-3-phenylpropanamide)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Piperidines)
RN  - 0 (Protease Inhibitors)
RN  - EC 3.4.11.2 (CD13 Antigens)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - CD13 Antigens/*antagonists & inhibitors/metabolism
MH  - Carcinoma, Lewis Lung/*drug therapy/enzymology/pathology/secondary
MH  - Cell Growth Processes/drug effects
MH  - Female
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neoplasm Metastasis
MH  - Piperidines/*pharmacology
MH  - Protease Inhibitors/pharmacology
EDAT- 2011/12/22 06:00
MHDA- 2012/07/28 06:00
CRDT- 2011/12/22 06:00
PHST- 2011/10/08 00:00 [received]
PHST- 2011/12/05 00:00 [accepted]
PHST- 2011/12/22 06:00 [entrez]
PHST- 2011/12/22 06:00 [pubmed]
PHST- 2012/07/28 06:00 [medline]
AID - 10.1007/s00280-011-1799-1 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2012 Apr;69(4):1029-38. doi: 
      10.1007/s00280-011-1799-1. Epub 2011 Dec 21.