Salinomycin sodium salt (Sodium salinomycin), an antibiotic potassium ionophore, is an effective inhibitor of Wnt/β-catenin signaling.

Salinomycin (0.1-8 μM) 对 HUVECs 生长的抑制作用呈剂量依赖性，分别在 4 和 8 μM 时抑制率达到 32.1% 和 59.2%。在 2、4 和 8 μM Salinomycin 作用 48 h 后，HUVECs 显示出剂量依赖的细胞数量减少和细胞形态改变。Salinomycin (4 μM) 处理有效抑制 HUVEC 迁移和侵袭，并显著破坏 HUVECs 的类毛细管管腔形成。Salinomycin 显著以时间和剂量依赖的方式抑制了 HUVECs 中磷酸化 (p)-FAK 的表达水平。通过干扰 VEGF-VEGFR2-AKT 信号轴，Salinomycin 抑制 HUVEC 血管生成 [1]。RSVL 与 Salinomycin 的联合使用在 TNBC (MDA-MB-231) 细胞中协同抑制增殖。RSVL 和 Salinomycin 有效降低 TNBC 细胞的伤口愈合、集落形成和肿瘤球形成能力 [2]。Salinomycin (0、2、4、8 和 16 μM) 在剂量和时间依赖的方式下显著抑制 A2780 和 SK-OV-3 细胞系的增殖，分别在 24h、48h 和 72h，IC50 值分别为 A2780 细胞系的 13.8、6.888 和 4.382 μM，SK-OV-3 细胞系的 12.7、9.869 和 5.022 μM。Salinomycin 阻断 EOC 细胞中的 Wnt/β-catenin 通路 [3]。Salinomycin (2 μM) 降低癌细胞增殖，抑制 STAT3 磷酸化和 P38 及 β-catenin 表达，并抑制结直肠癌细胞的上皮-间质转化。Salinomycin (1-5 μM) 抑制结直肠癌细胞的增殖和 STAT3 信号传导，并且在 HT-29 和 SW480 中激活 Akt (Ser 473)、下调 Hsp27 (Ser 82) 磷酸化。当与端粒酶抑制剂联用时，Salinomycin 下调 hTERT 并减少端粒酶活性 [4]。

Salinomycin（5和10 mg/kg）显著抑制了平均肿瘤体积和肿瘤重量。Salinomycin通过抑制血管生成以及AKT和FAK去磷酸化的过程，阻碍了U251人类胶质瘤细胞在体内的生长[1]。Salinomycin（0.5 mg/kg b.wt.）提高了携带肿瘤的瑞士白鼠的平均存活时间[2]。

Briefly, HUVECs (6,000 cells/well) are seeded in 96-well culture plates for 24 h and incubated with different concentrations of Salinomycin. In the preliminary experiments, Salinomycin treatment for 12, 24, 48 and 72 h shows time-dependent effects on cell growth inhibition. However, treatment for 48 h is the optimal time and is selected for further mechanism evaluation. After Salinomycin treatment for 48 h, 20 μL/well of MTT solution (5 mg/mL) is added and incubated for 5 h. The medium is aspirated and replaced with 200 μL/well of DMSO to dissolve the formazan Salinomycint formed. The color intensity of the formazan solution is measured at 570 nm by a microplate spectrophotometer. The cell viability is expressed as % of the control (as 100%) [1].

Human glioma U251 cells (1×10^7) suspended in 100 μL PBS are injected into the right lower hind flank of each 6-week-old male nude mouse. The mice are then randomly assigned into three groups of 10 mice in each group. After one week, Salinomycin (5 and 10 mg/kg) is administered into the caudal vein every other day for 16 days. Control mice receive an equal volume of vehicle (Salinomycinine) only. Bodyweight and tumor volume are monitored every two days. At the end of the experiments, tumors are excised, photographed, and weighed. Tumors from each group are used for western blotting and immunohistochemical assay [1].