ABSTRACT
CCN1, a secreted matrix-associated molecule, is involved in multiple cellular processes. Previous studies have indicated that expression of CCN1 correlates inversely with the aggressiveness of non-small-cell lung carcinoma (NSCLC); however, the underlying mechanisms remain elusive. Using three NSCLC cell line systems, here we show that long-term treatment of cells with the recombinant CCN1 protein led to a permanent cell cycle arrest in G1 phase; cells remained viable as judged by apoptotic assays. CCN1-treated NSCLC cells acquired a phenotype characteristic of senescent cells, including an enlarged and flattened cell shape and expression of the senescence-associated ß-galactosidase. Immunoblot analysis showed that addition of CCN1 increased the abundance of hypo-phosphorylated Rb, as well as accumulation of p53 and p21. Silencing the expression of p53 or p21 by lentivirus-mediated shRNA production in cells blocked the CCN1-induced senescence. Furthermore, a CCN1 mutant defective for binding integrin α6ß1 and co-receptor heparan sulfate proteoglycans was incapable of senescence induction. Our finding that direct addition of CCN1 induces senescence in NSCLC cells provides a potential novel strategy for therapeutic intervention of lung cancers.
Subject(s)
Cellular Senescence/drug effects , Cysteine-Rich Protein 61/pharmacology , Lung Neoplasms/metabolism , Blotting, Western , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cyclin-Dependent Kinase Inhibitor p21 , Humans , Signal Transduction/drug effectsABSTRACT
OBJECTIVE: To study the ratio between soft and hard tissue on the horizontal plane after the operations of maxillary Le Fort I advancement osteotomy and mandibular setback osteotomy in patient with skeletal class III malformations. It can help to predict precisely the post-operational profile. METHODS: 20 patients with skeletal class III malformation were taken cephalometric films pre-and post-operationally. The coordinate of landmarks were given from two films by computer analysis system. Different values in X axis were analysed statistically. RESULTS: All mandibular soft tissue landmarks were correlated with hard tissue landmarks (r<0.5, P>0.05). The ratios were 1:1 except the Pogonion(<1:1). Point of Sn was not correlated with the maxillary hard tissue significantly(r<0.5, P>0.05). CONCLUSION: The poor correlation between maxillary Sn and hard tissue was affected by many factors. It is easy to mark the mandible landmarks clearly. The ratio should help to predict the post-operation profile in patients with skeletal class III malformations.
