Promyelocytic leukemia (APL) patients ( 13). Zinc finger 2 (GLI2) prevents osteosarcoma growth and invasionĪrsenic trioxide (ATO) is a Food and DrugĪdministration (FDA)-approved reagent that is used to treat acute Others reported that inhibition of smoothened (SMO) or GLI family Transcription of target genes, including GLI1, HHIP, PTCH1, CYCLIN Of smoothened (SMO), which then leads to nuclear translocation andĪctivation of GLI transcription factors (GLI1/-2/-3). Indian, and desert Hedgehog) to patched1 (PTCH1) promotes release The Hedgehog pathway plays important roles inĮmbryonic development and adult organ homeostasis and regeneration Have investigated the function of the Hedgehog pathway in Mechanisms of osteosarcoma growth and metastasis. Prognosis, many investigators have researched the molecular To establish new chemotherapies to improve Metastatic osteosarcoma exhibits resistance to standard With osteosarcoma have a strong tendency of lung metastasis. Long-term prognosis for non-metastatic disease to ~50–80% ( 3). High-dose chemotherapy and surgical intervention have improved Malignant tumor of the bone in children and adolescents ( 1, 2). Osteosarcoma is the most commonly diagnosed primary Our findings indicate that combination of Hedgehog pathway inhibitors and standard FDA-approved anticancer agents with established safety for human use may be an attractive therapeutic method for treating osteosarcoma. An osteosarcoma xenograft model showed that treatment with ATO and CDDP, IFO, or vismodegib significantly prevented osteosarcoma growth in vivo compared with vehicle treatment. Combination of ATO and CDDP, IFO, DOX or vismodegib was synergistic when the two compounds were used on proliferating 143B and Saos2 human osteosarcoma cells. WST-1 assays showed that 143B and Saos2 cell proliferation was inhibited by ATO combined with CDDP, IFO, DOX, and vismodegib. Xenograft models were used to examine the synergism in vivo. Combination-index (CI) was used to examine synergism using CalcuSyn software. We performed WST-1 assays using ATO, cisplatin (CDDP), ifosfamide (IFO), doxorubicin (DOX), and vismodegib. To apply our previous findings in clinical settings, we examined the effects of Hedgehog inhibitors including arsenic trioxide (ATO) and vismodegib combined with standard anticancer agents. We and others have investigated the function of Hedgehog pathway in osteosarcoma. However, metastatic osteosarcoma exhibits resistance to standard chemotherapy. High-dose chemotherapy and surgical intervention have improved long-term prognosis for non-metastatic osteosarcoma to 50-80%.
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