FIM-A, a phosphorus-containing sirolimus, inhibits the angiogenesis and proliferation of osteosarcomas.

摘要: The mTOR pathway is a central control of cell growth, proliferation, metabolism, and survival, deregulated in most cancers. Cancer cells are addicted to increased activity kinase-mediated signaling pathways, leading numerous inhibitors preclinic clinical trials for cancer therapy. Phosphorus-containing sirolimus (FIM-A), which targets signaling, inhibits growth vitro. Here we report that FIM-A reduces the angiogenesis proliferation osteosarcoma both vitro vivo. In cultured lines, inhibited arrested G1 phase cycle, accompanied with reduction VEGF HIF-1alpha. With vivo mouse xenografts, treatment resulted inhibition mTORC1 as demonstrated by decreased phosphorylation p70S6K1 4E-BP1. Consistent this finding, significantly average tumor volume, nuclei staining PCNA, number intratumoral microvessels. Our data targeting vivo, providing basis further development therapy patients.