Endostar, a modified endostatin inhibits non small cell lung cancer cell in vitro invasion through osteopontin-related mechanism

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• 作者：Qinggui Ni ; Hui Ji ; Zhihui Zhao ; Xin Fan ; Chengyun Xu
• 关键词：Endostar ; Osteopontin ; Non-small cell lung cancer ; In vitro invasion ; CD44v6 ; α ; _Vβ ; ₃ integrin ; Matrix metalloproteinase
• 刊名：European Journal of Pharmacology
• 出版年：2009
• 出版时间：1 July 2009
• 年：2009
• 卷：614
• 期：1-3
• 页码：1-6
• 全文大小：516 K

文摘

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 α_Vβ₃ 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.