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Abstract: Objective To investigate the effect of jatrorrhizine on the development of osteosarcoma and its mechanism. Methods The targets of jatrorrhizine on osteosarcoma were screenedthrough network pharmacology analysis, and GSEA enrichment was used to analyze the relationshipbetween the expression level of monoamine oxidase B (MAOB) and the clinical phenotypes of osteosarcoma. The cell activities of osteosarcoma cells MG63 and U2OS were detected under differentdoses of jatrorrhizine (0, 2, 4, 8, 16 μmol / L), and the optimal jatrorrhizine dose for follow-upfunctional test was selected. CCK-8 method and Transwell assay were used to detect the cell proliferation, migration and invasion of MG63 and U2OS, and Western blotting was applied to detect theprotein expression levels of cell proliferation-associated antigen Ki67, matrix metalloproteinase 2(MMP2) and MMP9. The subcutaneous transplant models of osteosarcoma in nude mice were established, and the weight and volume of tumor tissues of each group were measured, and the expression level of Ki67 was determined by immunohistochemistry. Western blotting was adopted to detect the effect of jatrorrhizine on the expression level of MABO protein in osteosarcoma cells. shRNA was used to interfere with the expression of MAOB, and its effect on the proliferation of osteosarcomacells was analyzed. Results Ten targets of jatrorrhizine on osteosarcoma, including MAOB, waspredicted by network pharmacology analysis. GSEA enrichment analysis showed that MAOB was related to the prognosis (P< 0. 05) and survival (log-rank P < 0. 05) of osteosarcoma. The viabilityof MG63 and U2OS cells decreased with the increase of the drug dose. The dose of 8 μmol / L was chosen for the follow-up functional test as the viability of osteosarcoma cells decreased by about50 % when the dose of jatrorrhizine reached 8 μmol / L. In vitro experiment showed that comparedwith those in the Control group, the cell proliferation rate of jatrorrhizine group was significantly reduced (P < 0. 05), and the number of invasion cells and migrating cells were significantly decreased (P< 0. 05), and the protein levels of Ki67, MMP2 and MMP9 were significantly downregulated (P< 0. 05). In vivo experiment showed that the growth rate of subcutaneous tumors in nudemice of jatrorrhizine group was significantly reduced ( P < 0. 05), and the weight and volume ofsubcutaneous tumors were lowered (P < 0. 05), and the expression level of Ki67 in tumor tissueswas significantly declined (P< 0. 05). Jatrorrhizine inhibited the expression of MAOB in osteosarcoma cells in a time and concentration-dependent manner in vitro (P < 0. 05). Knockdown of MAOBcould significantly inhibit the proliferation of osteosarcoma cells when compared with shNC group(P< 0. 05). Overexpression of MAOB could reverse the inhibitory effect of jatrorrhizine on the proliferation, invasion and migration of osteosarcoma cells (P< 0. 05). Conclusion The expression level of MAOB is related to the prognosis and survival of osteosarcoma. MAOB promotes cell proliferation, invasion and tumor metastasis. Jatrorrhizine inhibits the proliferation, invasion and migrationof osteosarcoma cells by inhibiting the expression of MAOB.

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