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Inhibitory effect of rutin on the growth and metastasis of osteosarcoma in vitro and in vivo
Received date: 2024-04-25
Accepted date: 2024-08-19
Online published: 2025-01-17
Supported by
Sichuan Science and Technology Plan Project(20YYJC2032)
Objective ·To investigate the effects of rutin on proliferation, apoptosis, migration and invasion of osteosarcoma cells and its possible molecular mechanisms. Methods ·Human osteosarcoma MG63 and U2OS cells were treated with rutin at concentrations of 10, 20 and 40 μmol/L, respectively. The effects of rutin on proliferation, apoptosis, migration, and invasion of MG63 and U2OS cells were assessed by using CCK-8 assay, colony formation assay, flow cytometry, scratch closure assay, and Transwell assay. The expression levels of cell proliferation antigen Ki67, B-cell lymphoma-2 (Bcl-2), and Bcl-2 associated X protein (Bax) proteins were detected by Western blotting. Twelve BALB/c nude mice were subcutaneously injected with osteosarcoma MG63 cells to establish a subcutaneous transplant tumor model. The mice were randomly divided into two groups: a control group and a rutin 40 mg/kg group (6 mice in each group). The rutin 40 mg/kg group was intraperitoneally injected with rutin (40 mg/kg), and the control group was intraperitoneally injected with an equal volume of saline, once every other day for 4 weeks. The tumor volume was measured every week. After 4 weeks, the mice were euthanized, and the tumors were excised and weighed. Immunohistochemistry was used to detect the expression of Ki67 and vascular endothelial growth factor (VEGF) in tumor tissues. TUNEL was used to detect tumor cell apoptosis. Results ·Compared with MG63 and U2OS cells not treated with rutin, MG63 and U2OS cells treated with rutin at 20 and 40 μmol/L showed a significant decrease in proliferation rate, an increase in apoptotic rate, a decrease in migration and invasion abilities, a significant downregulation of Ki67 protein, and a significant increase in Bax/Bcl-2 ratio, with statistically significant differences (all P<0.05). In addition, rutin significantly inhibited the in vivo growth of osteosarcoma cells, reduced the expression of Ki67 and VEGF in tumor tissues, and promoted cell apoptosis (all P<0.05). Conclusion ·Rutin can inhibit the proliferation, migration, and invasion of osteosarcoma cells, and promote apoptosis.
Key words： rutin; osteosarcoma; proliferation; invasion; cell proliferation antigen Ki67
LI Xiang , WEI Ming , WU Wenxi , LUO Xiaoqin , YAO Biao , WU Siyu . Inhibitory effect of rutin on the growth and metastasis of osteosarcoma in vitro and in vivo[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025 , 45(1) : 20 -28 . DOI: 10.3969/j.issn.1674-8115.2025.01.003
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