Cancer Therapy: Preclinical Aspirin Suppresses the Growth and Metastasis of Osteosarcoma through the NF-kB Pathway

Purpose: Aspirin has recently been reported to reduce both the incidence and the risk of metastasis in colon cancer. However, there is no evidence at the cellular levels or in the animal models for such an effect of aspirin on cancer metastasis. Experimental Design:MTT assay, colony formation assay, and apoptosis assaywere employed to analyze the effects of aspirin on the osteosarcoma cell viability in vitro. The NF-kB activity was measured by the NF-kB p65 luciferase reporter. Western blotting was used to analyze the proteins in cells. The migration and invasion abilities of osteosarcoma cells in vitro were measured by the Transwell assay. Xenograft-bearingmicewere used to assess the roles of aspirin in both tumor growth and metastasis of osteosarcoma in vivo (n1⁄4 5–8mice/group). An unpaired Student t test or ANOVAwith the Bonferroni post hoc test were used for the statistical comparisons. Results: Aspirin reduced cell viability in a doseand timedependent manner in osteosarcoma cell lines, and aspirin synergistically sensitized osteosarcoma cells to cisplatin (DDP) in vitro and in vivo (P < 0.001). Moreover, aspirin markedly repressed the migration and invasion of osteosarcoma cells in vitro (P < 0.001), and dramatically diminished the occurrence of osteosarcoma xenograft metastases to the lungs in vivo (P < 0.001). Mechanistically, aspirin diminishes osteosarcoma migration, invasion, and metastasis through the NF-kB pathway. Conclusions: Aspirin suppresses both the growth and metastasis of osteosarcoma through theNF-kBpathway at the cellular level and in the animal models. Clin Cancer Res; 21(23); 5349–59. 2015 AACR.