MEK inhibition preferentially suppresses anchorage‐independent growth in osteosarcoma cells and decreases tumors in vivo

摘要: Osteosarcoma is the most common high-grade malignancy of bone, and novel therapeutic options are urgently required. Previously, we developed mouse osteosarcoma AXT cells that can proliferate both under adherent nonadherent conditions. Based on metabolite levels, conditions were more similar to in vivo environment than A drug screen identified MEK inhibitors, including trametinib, preferentially decreased viability cells. Trametinib inhibited cell cycle induced apoptosis cells, effects stronger also potently U2OS but its less prominent MG63 or Saos2 By contrast, sensitive PI3K inhibition Notably, combination MAPK/ERK kinase (MEK) synergistically this effect was pronounced Therefore, signal dependence for survival crosstalk between MEK-ERK PI3K-AKT pathways context-dependent. The activation status other kinases CREB varied a context-dependent manner, which might determine response inhibition. single dose trametinib sufficient decrease size primary tumor circulating vivo. Moreover, combined administration rapamycin conventional anticancer drugs further increased antitumor activity. Thus, given optimal biomarkers predicting effects, holds potential treatment osteosarcoma.