PMID- 19389394
OWN - NLM
STAT- MEDLINE
DCOM- 20090825
LR  - 20181201
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 614
IP  - 1-3
DP  - 2009 Jul 1
TI  - Endostar, a modified endostatin inhibits non small cell lung cancer cell in vitro 
      invasion through osteopontin-related mechanism.
PG  - 1-6
LID - 10.1016/j.ejphar.2009.04.032 [doi]
AB  - In this study, we studied the inhibition of non small cell lung cancer (NSCLC) 
      cells invasion by a recombinant human Endostar, a modified endostatin and the 
      possible osteopontin-related mechanism. The results showed that Endostar 
      significantly inhibited highly metastatic NSCLC (NCI-H460) cells in vitro 
      invasion. ELISA demonstrated that reduction of osteopontin level in the medium by 
      Endostar may be responsible for the inhibition of invasion. RT-PCR assay and 
      western blot analysis revealed that the reduction of osteopontin was due to 
      under-regulation of osteopontin expression. Furthermore, Endostar also inhibited 
      osteopontin-induced less metastatic NSCLC (A549) cells invasion, indicating that 
      Endostar may have other different osteopontin-related mechanism. In an adhesion 
      assay, we found that Endostar reduced NCI-H460 cells binding to osteopontin. Flow 
      cytometric analysis suggested that the reduction of adhesion may be related to 
      under-regulation of its receptors (CD44v6 and alpha(V)beta(3) integrin) 
      expression. Additionally, we found, via gelatin zymographic analysis, that 
      osteopontin-induced the expression and activation of pro-matrix metalloproteinase 
      (MMP)-2 and pro MMP-9 secreted from A549 cells were blocked upon Endostar 
      treatment, indicating that Endostar may block osteopontin-mediated signal 
      transduction pathways through MMP families. The above results indicate that 
      Endostar may have an intrinsic non-angiogenesis-related antitumor activity 
      through osteopontin-related mechanism against NSCLC, including osteopontin change 
      and osteopontin signal transduction blockade. Tumor cell invasion is important 
      for tumor metastasis, our findings suggest that it is probably a good strategy to 
      put Endostar into treatment of NSCLC metastasis.
FAU - Ni, Qinggui
AU  - Ni Q
AD  - Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, 
      China.
FAU - Ji, Hui
AU  - Ji H
FAU - Zhao, Zhihui
AU  - Zhao Z
FAU - Fan, Xin
AU  - Fan X
FAU - Xu, Chengyun
AU  - Xu C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090421
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Culture Media)
RN  - 0 (Endostatins)
RN  - 0 (Recombinant Proteins)
RN  - 106441-73-0 (Osteopontin)
RN  - EC 3.4.- (Metalloproteases)
RN  - GVG18ZDN65 (endostar protein)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Carcinoma, Non-Small-Cell Lung/genetics/*metabolism/*pathology
MH  - Cell Line, Tumor
MH  - Culture Media
MH  - Down-Regulation/drug effects
MH  - Endostatins/*pharmacology
MH  - Enzyme Activation/drug effects
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Lung Neoplasms/genetics/*metabolism/*pathology
MH  - Metalloproteases/genetics/metabolism
MH  - Osteopontin/genetics/*metabolism
MH  - Recombinant Proteins
EDAT- 2009/04/25 09:00
MHDA- 2009/08/26 09:00
CRDT- 2009/04/25 09:00
PHST- 2008/12/04 00:00 [received]
PHST- 2009/04/07 00:00 [revised]
PHST- 2009/04/09 00:00 [accepted]
PHST- 2009/04/25 09:00 [entrez]
PHST- 2009/04/25 09:00 [pubmed]
PHST- 2009/08/26 09:00 [medline]
AID - S0014-2999(09)00347-1 [pii]
AID - 10.1016/j.ejphar.2009.04.032 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2009 Jul 1;614(1-3):1-6. doi: 10.1016/j.ejphar.2009.04.032. Epub 
      2009 Apr 21.