Expression and clinical significance of Semaphorin4D in non-small cell lung cancer and its impact on malignant behaviors of A549 lung cancer cells.

This study aimed to explore Semaphrin4D (Sema4D) expression and clinical significance in non-small cell lung cancer (NSCLC), and to define the roles and mechanisms of Sema4D in regulating the malignant behaviors of A549 cells by small interfering RNA (siRNA). Firstly, immunohistochemistry revealed that Sema4D was more frequently expressed in NSCLC than in lung benign lesion (P<0.05) and its overexpression was associated with low differentiation (P<0.05), poor pTNM staging (P<0.05) and occurrence of lymph node (LN) metastasis (P<0.05). Endogenous Sema4D expression was suppressed by Sema4D siRNA in A549 cells overexpressing Sema4D. Protein levels of Sema4D, total Akt and p-Akt were examined by Western blotting. Cell proliferation, migration and invasion abilities were measured by MTT assay and Transwell assay respectively. Results showed that Sema4D siRNA significantly suppressed phosphorylation of AKT in A549 cells, but it did not alter total AKT expression. In addition, efficient down-regulation of SemaD significantly inhibit cell proliferation (P<0.05), migration (P<0.05) and invasion (P<0.05) in A549 cells. These findings suggest that Sema4D might serve as a reliable tool for early prediction of NSCLC poor prognosis. Sema4D could play an important role in promoting tumor proliferation, migration and metastasis in the NSCLC, by influencing the Akt protein phosphorylation. Inhibition of Sema4D may be a useful approach for the treatment of NSCLC.