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Figure 7 from Targeted Degradation of SOS1 Exhibits Potent Anticancer Activity and Overcomes Resistance in KRAS-Mutant Tumors and BCR–ABL–Positive Leukemia

作者:Ziwei Luo, Chencen Lin, Chuwei Yu, Changxian Yuan, Wenyong Wu, Xiaowei Xu, Renhong Sun, Yan Jia, Yafang Wang, Jie Shen, Dingyan Wang, Sinan Wang, Hualiang Jiang, Biao Jiang, Xiaobao Yang, Chengying Xie · 年份:2025 · DOI:10.1158/0008-5472.28122526 · 研究领域:Chronic Myeloid Leukemia Treatments、Chronic Lymphocytic Leukemia Research、Acute Lymphoblastic Leukemia research

<p>Combination of SIAIS562055 and TKIs synergistically inhibits the growth of CML xenografts <i>in vivo</i> and enhances cell death in primary samples from patients with CML. <b>A–D,</b> K562-xenografted mice received vehicle, SIAIS562055 (30 mg/kg/day), imatinib (100 mg/kg/day), or their combination; then, relative tumor volumes (<b>A</b>), tumor weights (<b>B</b>), photo of tumors (<b>C</b>), and mice body weights (<b>D</b>) were determined at indicated times. Data are presented as mean ± SEM, <i>n</i> = 5. <b>E,</b> Western blot analysis of SOS1, pERK, and pSTAT5 in K562 xenograft tumors after treatment with vehicle, SIAIS562055, imatinib, or their combination. Data are shown as mean ± SEM, <i>n</i> = 5. <b>F,</b> Cell viability of three primary BCR–ABL<sup>+</sup> samples from patients with CML treated with varying doses of SIAIS562055 or imatinib, alone or in combination, for 72 hours was assessed by CellTiter-Glo assay. Data are presented as mean ± SD, <i>n</i> = 3. <b>G,</b> Western blot analysis of the indicated proteins in primary samples from patients with CML under 24-hour exposure to SIAIS562055 or imatinib, alone or in combination. Statistical significance was assessed using two-tailed unpaired Student <i>t</i> test. *, <i>P</i> < 0.05; **, <i>P</i> < 0.01; ***, ...