Abstract
BACKGROUND: Anti-angiogenesis has been demonstrated to have a critical role in lung cancer pathogenesis. Here, we characterized the effect of the small-molecule angiogenesis inhibitor pazopanib on non-small cell lung cancer (NSCLC) cells. METHODS: NSCLC cells were tested for viability and migration after incubation with varying concentrations of pazopanib. Further, the phosphorylation status of extracellular signal-regulated kinase, protein kinase B, and MEK were assessed in vitro. For in vivo testing, mice grafted with NSCLC cell lines L9981 and A549 were treated orally with pazopanib. RESULTS: Pazopanib inhibits signaling pathways in tumor cells, thus blocking NSCLC cell growth and migration in vitro and inducing tumor cell arrest at G0/G1 phase. We show that pazopanib could inhibit tumor cell growth, decrease metastases, and prolong survival in two mouse xenograft models of human NSCLC. CONCLUSION: These preclinical studies of pazopanib show the possibility of clinical application and, ultimately, improvement in patient outcome.