Summary: | Yuanjue Sun,1,* Liguo Liu,2,* Yaling Wang,3 Aina He,3 Haiyan Hu,3 Jianjun Zhang,3 Mingyong Han,1 Yujing Huang3 1Cancer Therapy and Research Center, Shandong Provincial Hospital, Shandong University, 250021, Shandong, People’s Republic of China; 2Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 200233 Shanghai, People’s Republic of China; 3Department of Medical Oncology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 200233 Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: The aims of this study were to determine the effect of curcumin on osteosarcoma (OS) cells due to inactivation of the p-JAK2/p-STAT3 pathway and evaluate the prognostic value of this pathway in OS. Materials and methods: We exposed a human OS cell line (MG-63) to different concentrations of curcumin. Then, we characterized the effects on MG-63 cells using assays (cell viability, colony formation, cell cycle, wound healing, invasion), flow cytometry, Western blot, immunohistochemical analyses, and tumor xenograft. Results: The half-maximal inhibitory of curcumin for MG-63 cells at 24 hours was 27.6 µM. The number of colonies of MG-63 cells was decreased obviously upon curcumin (10 and 20 µM) treatment. We also found increased accumulation of MG-63 cells in the G2/M phase upon curcumin (10 and 20 µM) treatment. Apoptosis was increased in 10 and 20 µM curcumin-treated MG-63 cells. After incubation of physically wounded cells for 24 hours, the percentage wound width increased upon curcumin exposure. Curcumin obviously decreased the expression of pJAK-2 and pSTAT-3 in MG-63 cells in a dose-dependent manner. Curcumin dose-dependently inhibited the proliferation, migration, and invasion of MG-63 cells and induced arrest of the G0/G1 phase and apoptosis by inhibiting the p-JAK2/p-STAT3 pathway. The linear correlativity between expression of p-JAK2 and STAT3 was very prominent, and both were closely associated with lung metastasis. In vivo study suggested that curcumin suppressed tumor growth through JAK2/STAT3 signaling. Conclusion: Curcumin-mediated inhibition of the proliferation and migration of MG-63 cells was associated with inactivation of JAK/STAT signaling. Keywords: osteosarcoma, curcumin, multiplication, invasion
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