Figure 6 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：10.1158/0008-5472.28122529 · 研究领域：Chronic Myeloid Leukemia Treatments、Chronic Lymphocytic Leukemia Research、Acute Lymphoblastic Leukemia research

SIAIS562055 sensitizes CML cell lines to TKIs in vitro. A, SIAIS562055 and TKIs had synergistic effects on the proliferation of K562 and KU812 cells after treatment of 72 hours. Histogram shows the CI values. B, Cell apoptosis (Annexin V+) of the K562 and KU812 cells treated with SIAIS562055, TKIs such as imatinib, nilotinib, or olverembatinib (olvere), alone or in combination, for 48 hours. C, Western blot analysis of P-BCR–ABL, pSTAT5, SOS1, pERK, and cleaved caspase-3 in K562 and KU812 cells treated with SIAIS562055 or TKIs, alone or in combination. D, Western blot analysis of SLC22A4 in K562 and KU812 cells treated with SIAIS562055 (62.5 and 50 nmol/L, respectively) for 24 hours. E, High-performance liquid chromatography analysis examined the relative intracellular concentrations of imatinib (10 μmol/L in the media) in K562 and KU812 cells after being treated with SIAIS562055 (1,000 nmol/L, 24 hours) or SOS1 siRNAs (50 nmol/L, 48 hours). F, Cell viability of K562 treated with SLC22A4 siRNAs (25 nmol/L), SIAIS562055 (125 nmol/L), or imatinib (25 nmol/L), alone or in combination, for 72 hours was assessed by MTT assay. Data are presented as mean ± SD, n = 3. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ns, not significant.</p&g...