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. 2023 Jun 19;13:1192472. doi: 10.3389/fonc.2023.1192472

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Copyright © 2023 Xu, Chen, Sun, Shi, Wang, Huang, Ren and Tang

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Combination therapy was more effective to suppress OS malignant progression by blocking IL-6/STAT3 axis. (A) The migration ability of anlotinib-resistant OS cells was significantly inhibited by the combination treatment with tocilizumab. (B, C) The statistical plots showed the combination treatment with tocilizumab decreased the healing rate of anlotinib-resistant cells, and migration ability of anlotinib-resistant KHOS cells could also be inhibited by tocilizumab monotherapy. (D) The results of transwell assay showed the migration ability of anlotinib-resistant OS cells was significantly inhibited by the combination treatment. (E) The statistical data of transwell assay for 143B-R and KHOS-R cells. (F) Western blot results showed the EMT-related protein N-cad expression and vimentin expression were decreased which was caused by combination treatment. (G) The combination treatment with tocilizumab inhibited cytoskeleton formation of anlotinib-resistant OS cells. (H) Western blot results showed the STAT3 expression and phosphorylation were inhibited because of the combination treatment. (ns, no significance; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001).