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Sorafenib (SRF) is a multi-kinase inhibitor that has been shown to have antitumor activity against several types of cancers, but the effect of SRF on EBV-transformed B cells is unknown. We report that SRF can induce the apoptosis of EBV-transformed B cells through JNK/p38-MAPK activation. SRF triggered the generation of reactive oxygen species (ROS), translocation of Bax into the mitochondria, disruption of mitochondrial membrane potential, activation of caspase-9, caspase-3 and PARP, and subsequent apoptosis. Moreover, we found that SRF exposure activated the phosphorylation of JNK and p38-MAPK and suppressed the phosphorylation of PI3K-p85 and Akt. N-acetyl-l-cysteine (NAC) inhibited the activation of JNK and p38-MAPK. SP600125 and SB203580 blocked apoptosis and mitochondrial membrane disruption but did not affect ROS production after SRF treatment. These findings provide novel insights into the molecular mechanisms driving SRF-mediated cell death and suggest that SRF could be a potential therapeutic drug for the treatment of EBV-related malignant diseases.

Galectin-3 is involved in tumor cell proliferation, adhesion, angiogenesis and metastasis. Galectin-3 promotes β-catenin/Wnt signaling, and β-catenin-related oncogenesis has been frequently reported in osteosarcoma. However, the correlation between galectin-3 and β‑catenin signaling in osteosarcoma is poorly defined. We hypothesized that galectin-3 may control the migration and invasion of cancer cells and that silencing of galectin-3 would therefore, suppress motility in osteosarcoma cells. In the present study, we show that galectin-3 silencing in cultured human osteosarcoma cells had decreased cell migration and invasion capabilities; reduced the expression and activation of FAK, Src, Lyn, PI3K/Akt, ERK1/2 and β-catenin, which are key mediators of invasion; inhibited the expression and secretion of VEGF, MCP-1, IL-8, IL-6, MMP2/9 and phospho-Stat3; and potentiated sensitivity to cisplatin. Our results suggest that galectin-3 may be a feasible therapeutic target for osteosarcoma.

IL-18 has recently been reported to play a critical role in tumor migration, invasion, and metastasis. Because IL-18 has various biological activities after its secretion as an 18 kDa mature form, the regulation of the IL-18 secretion process is an important step in tumor progression. This study investigated the implication of IL-18 in vascular endothelial growth factor (VEGF)-D-regulated migration, along with the role of the IL-18 secretion process. VEGF-D enhanced cell migration, which was then blocked by inhibiting IL-18. VEGF-D increased IL-18 expression and secretion, suggesting that IL-18 is a critical mediator for VEGF-D-enhanced migration. VEGF-D induced a disintegrin and metalloprotease 33 (ADAM33) expression, which has a metalloproteinase domain. VEGF-D-enhanced IL-18 secretion and cell migration were inhibited by ADAM33 knock-down. Moreover, cell proliferation was considerably reduced in ADAM33 small interfering RNA transfectants. In conclusion, ADAM33 has a key role in gastric cancer pathogenesis by up-regulating IL-18 secretion process, resulting in increased cell migration and proliferation.

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