Genistein and trichostatin A (TSA) are two chemotherapeutic compounds with antitumor effects in different types of cancer cell. However, the effects of genistein and TSA on the HEp-2 laryngeal cancer cell line remain to be fully elucidated. In the present study, it was found that genistein and TSA inhibited cell growth and cell migration, and promoted apoptosis in the HEp-2 laryngeal cancer cell line. The HEp-2 cells were treated with genistein, TSA or the two compounds in combination. Cell proliferation and apoptosis were measured using an MTT assay, Annexin V/propidium iodide staining and a TUNEL assay. Cell invasion was determined using a Matrigel-based Transwell assay. Western blotting was used to examine the activation of the Akt pathway and the expression levels of pro-or anti-apoptotic proteins. Treatment with either genistein or TSA alone mildly inhibited cell viability, growth and invasion, and induced the apoptosis of the laryngeal cancer cells, whereas more marked effects were observed in the cells treated with the combination of the two compounds. In addition, genistein reversed endothelial growth factor-induced epithelial-mesenchymal transition (EMT) in the HEp-2 cells, the effect of which were was further increased by joint application with TSA. Treatment of the HEp-2 cells with genistein and TSA led to a significant reduction in the phosphorylation of Akt and activation of its downstream target, and resulted in peroxisome proliferator-activated receptor-γ cleavage, increased expression of B cell lymphoma-2 (Bcl-2)-associated X protein and reduced the expression of Bcl-2. In conclusion, the present study demonstrated that, with the involvement of TSA, genistein exhibited substantial advantages in inhibiting laryngeal carcinoma cell growth, invasion and EMT, and induced apoptosis, compared with genistein treatment alone, which occurred through the regulation of Akt activation and the apoptotic pathway.

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7666 Background: Bone sialoprotein (BSP) and osteopontin (OPN) have been demonstrated predictive of bone metastases in breast and prostate carcinoma, consistent with the proposed role of BSP as a stimulator of bone mineralization and OPN in differentiation and activation of osteoclasts. Bone metastasis (BM) is often developed in non-small-cell lung cancer (NSCLC), but no predictive biomarker was identified for high risk of metastatic bone dissemination. Methods: 180 completely resected NSCLC patients were included in this study. 38 patients subsequently developed BM. Paraffin embedded primary tumor tissue of patients were supplied to produce a tissue microarray, and immunohistochemistry method was used for evaluation the expression of BSP and OPN. Different expressions of these two biomarkers among BM group and non-BM group were estimated by χ2 test. Bone metastasis-free survival was analyzed by Kaplan-Meier method. The prognostic impact of clinicopathologic parameters and biomarker expression was evaluated by Cox propotional hazards model. Results: BSP expression was associated with BM (P=0.027), while OPN expression could not reach statistical significance (P=0.495). Univariate analysis demonstrated that expression of BSP (P=0.036), N stage (P=0.000) and clinical stage (P=0.001) were associated with time interval to BM. Multivariate analyses showed BSP expression (RR=1.779, P=0.012) and clinical stage (RR=1.620, P=0.005) were independent prognostic factors for BM. Conclusions: BSP protein expression in the primary resected NSCLC is strongly associated with BM and could be used to identify high-risk patients. Correlation of OPN protein expression and bone metastasis need further investigation. No significant financial relationships to disclose.