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. 2022 May 10;21:111. doi: 10.1186/s12943-022-01549-1

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — Establishment and verification of sunitinib-resistant models. A The graphical representation of sunitinib-resistant models. B CCK8 assay of sunitinib-resistant cell lines and control cell lines with sunitinib treatment at indicated concentrations for 48 h. C Colony formation assay of sunitinib-resistant cell lines and control cell lines with sunitinib treatment (2 uM) in 6-well dish for 3 weeks (n = 3). Representative images (left) and average number of colonies (right) are shown. D Tube formation assay of sunitinib-resistant cell lines and control cell lines in 48-well dish. Representative images (up) and total number of nodes and length (below) are shown. E EdU assay was applied to compare the cell proliferation ability in sunitinib-resistant cell lines and control cell lines with sunitinib treatment (7 uM for 78S/R, 5 uM for OSS/R) (scale bar, 100 μm). F Analysis of apoptosis in 78R, 78S, OSR and OSS cells with sunitinib treatment by flow cytometry (7 uM for 78S/R, 5 uM for OSS/R). G-I Tumor volume, tumor weight and tumor growth curve of CDX-S and CDX-R under sunitinib or vehicle treatment(40 mg/kg/day) for 30 days. J Immunohistochemistry for KI67, CD31 and CD105 comparing CDX-S and control CDX-R. Scale bar, 50 μm. Data are expressed as the mean ± SEM. Statistical analyses used Student’s t-test and Kaplan–Meier survival analysis. p < 0.05 was considered statistically significant. * p < 0.05, ** p < 0.01, *** p < 0.001 and **** p < 0.0001