Cheng Ngan Ching, van Zandwijk Nico, Reid Glen
Asbestos Diseases Research Institute, University of Sydney, Concord, New South Wales, Australia.
PLoS One. 2014 Mar 3;9(3):e90374. doi: 10.1371/journal.pone.0090374. eCollection 2014.
Malignant pleural mesothelioma (MPM) is an almost invariably fatal, asbestos-related malignancy arising from the mesothelial membrane lining the thoracic cavities. Despite some improvements in treatment, therapy is not considered curative and median survival following diagnosis is less than 1 year. Although still classed as a rare cancer, the incidence of MPM is increasing, and the limited progress in treating the disease makes the identification of new therapies a priority. As there is evidence for expression of the integrins αvβ3 and αvβ5 in MPM, there is a rationale for investigating the effects on MPM of cilengitide, a synthetic peptide inhibitor of integrin αv heterodimer with high specificity for αvβ3 and αvβ5. In mesothelial cells (MC) and 7 MPM cell lines, growth inhibition by cilengitide was associated with the expression level of its target integrins. Furthermore, cilengitide caused cell detachment and subsequent death of anoikis-sensitive cells. It also suppressed invasion of MPM cells in monolayer and three-dimensional cultures. Gene knockdown experiments indicated that these effects of cilengitide were, at least partly, due to antagonism of αvβ3 and αvβ5.
恶性胸膜间皮瘤（MPM）是一种几乎必然致命的、与石棉相关的恶性肿瘤，起源于胸腔内衬的间皮膜。尽管治疗方面有一些改善，但治疗并不被认为是治愈性的，诊断后的中位生存期不到1年。虽然MPM仍被归类为罕见癌症，但其发病率正在上升，且治疗该疾病进展有限，因此确定新的治疗方法成为当务之急。由于有证据表明MPM中存在整合素αvβ3和αvβ5的表达，因此有理由研究西仑吉肽（一种对αvβ3和αvβ5具有高特异性的整合素αv异二聚体合成肽抑制剂）对MPM的影响。在间皮细胞（MC）和7种MPM细胞系中，西仑吉肽的生长抑制作用与其靶整合素的表达水平相关。此外，西仑吉肽导致细胞脱离以及随后失巢凋亡敏感细胞的死亡。它还抑制了MPM细胞在单层和三维培养中的侵袭。基因敲低实验表明，西仑吉肽的这些作用至少部分归因于对αvβ3和αvβ5的拮抗作用。
