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Oncol Res. 2013;20(7):319-26.

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

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The First Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China.


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

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