Shichang Zhao1, Nanji Lu, Yimin Chai, Xingang Yu. 1. Department of Orthopedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai 200233, China.
Abstract
PURPOSE: Treatment options for osteosarcoma are limited due to its resistance to chemotherapy and radiotherapy. Signaling through the mammalian target of rapamycin (mTOR) pathway contributes to cell proliferation and chemoresistance of many cancers. Rapamycin, as an inhibitor of mTOR, has been developed as potentially valuable therapeutic agent. In this report, we evaluated the effects of rapamycin on human osteosarcoma cells' growth in vitro and in vivo. METHODS: Proliferation of osteosarcoma cells treated with rapamycin at different time periods was detected and changes in the cell cycle were measured by MTS and flow cytometry, respectively. Autophagy induced by rapamycin in osteosarcoma cells and the expression of cell cycle regulating proteins were detected by Western blotting. The effect of rapamycin on tumor growth in vivo was detected using mice xenograph models. RESULTS: The proliferation of osteosarcoma cells was signif- icantly inhibited by rapamycin treatment in a concentration-dependent manner and the cell cycle progression was impaired with G1 arrest. Rapamycin induced autophagy, increased the expression of p27 and decreased the expression of Cyclin D1. In addition, rapamycin suppressed the tumor growth in mice xenograph models. CONCLUSIONS: The potent antiproliferative activities of mTOR inhibitor rapamycin has been proven. Theses results strongly indicate that rapamycin may be a promising agent against osteosarcomas.
PURPOSE: Treatment options for osteosarcoma are limited due to its resistance to chemotherapy and radiotherapy. Signaling through the mammalian target of rapamycin (mTOR) pathway contributes to cell proliferation and chemoresistance of many cancers. Rapamycin, as an inhibitor of mTOR, has been developed as potentially valuable therapeutic agent. In this report, we evaluated the effects of rapamycin on humanosteosarcoma cells' growth in vitro and in vivo. METHODS: Proliferation of osteosarcoma cells treated with rapamycin at different time periods was detected and changes in the cell cycle were measured by MTS and flow cytometry, respectively. Autophagy induced by rapamycin in osteosarcoma cells and the expression of cell cycle regulating proteins were detected by Western blotting. The effect of rapamycin on tumor growth in vivo was detected using mice xenograph models. RESULTS: The proliferation of osteosarcoma cells was signif- icantly inhibited by rapamycin treatment in a concentration-dependent manner and the cell cycle progression was impaired with G1 arrest. Rapamycin induced autophagy, increased the expression of p27 and decreased the expression of Cyclin D1. In addition, rapamycin suppressed the tumor growth in mice xenograph models. CONCLUSIONS: The potent antiproliferative activities of mTOR inhibitor rapamycin has been proven. Theses results strongly indicate that rapamycin may be a promising agent against osteosarcomas.
Authors: Amy K LeBlanc; Timothy M Fan; Christina N Mazcko; Aswini Cherukuri; Erika P Berger; William C Kisseberth; Megan E Brown; Susan E Lana; Kristen Weishaar; Brian K Flesner; Jeffrey N Bryan; David M Vail; Jenna H Burton; Jennifer L Willcox; Anthony J Mutsaers; J Paul Woods; Nicole C Northrup; Corey Saba; Kaitlin M Curran; Haley Leeper; Heather Wilson-Robles; Brandan G Wustefeld-Janssens; Stephanie Lindley; Annette N Smith; Nikolaos Dervisis; Shawna Klahn; Mary Lynn Higginbotham; Raelene M Wouda; Erika Krick; Jennifer A Mahoney; Cheryl A London; Lisa G Barber; Cheryl E Balkman; Angela L McCleary-Wheeler; Steven E Suter; Olya Martin; Antonella Borgatti; Kristine Burgess; Michael O Childress; Janean L Fidel; Sara D Allstadt; Daniel L Gustafson; Laura E Selmic; Chand Khanna Journal: Clin Cancer Res Date: 2021-03-22 Impact factor: 13.801