Stimulatory effects of sorafenib on human non‑small cell lung cancer cells in vitro by regulating MAPK/ERK activation

Sorafenib is an inhibitor of a number of intracel- lular signaling kinases with antiproliferative, anti-angiogenic and pro-apoptotic effects in tumor cells. Sorafenib has been used in the therapy of advanced renal cell carcinoma. In the present study, using two human non-small cell lung cancer (NSCLC)cell lines, A549 and NCI-H1975, the effects of sorafenib on proliferation, apoptosis and intracellular signaling were systematically characterized. The results revealed that at a low concentration (5 µM) and early time point (6 h), sorafenib is capable of significantly stimulating proliferation of A549 cells, but not NCI-H1975 cells. In addi- tion, the comparison of the two cell lines revealed different cell cycle redistribution and apoptotic susceptibility to sorafenib at this concentration and time point. Western blot analysis revealed that sorafenib upregulated the expression of cyclin D1 and cyclin-dependent kinase 2 and downregulated the expression of BAX at this specific point. Furthermore, sorafenib was confirmed to regulate the expression of cyclin D1 and apoptosis-associated proteins through the regulation of extracellular signal-regulated kinase 1/2 phosphorylation in A549 cells. These findings suggest that, although sorafenib has the potential for use in the treatment of renal cell carcinoma, this compound may also activate NSCLC cells at a specific time point.