| In Vitro |
SCFSkp2-IN-2 (Compound AAA-237) (0.3-3 μM; 24-72 h) 可直接与 Skp2 结合，导致 Skp2 被蛋白酶体降解。AAA-237 对 Skp2 mRNA 表达无显著影响，但对 NSCLC 细胞中 Skp2 蛋白表达有时间依赖性的抑制作用[1]。 SCFSkp2-IN-2 (0.3-3 μM; 24-72 h) 以剂量和时间依赖的方式抑制 A549 和 H1299 细胞的增殖[1]。 SCFSkp2-IN-2 (0.3-3 μM; 24-72 h) 通过调节 Skp2-Cip/Kip 和 PI3K/Akt-FOXO1 信号通路，在 G0/G1 检查点阻止细胞周期[1]。 SCFSkp2-IN-2 (0.3-3 μM; 24-72 h) 以剂量和时间依赖的方式诱导 A549 和 H1299 细胞凋亡[1]。 SCFSkp2-IN-2 (0.3 μM; 1-7 days) 诱导 NSCLC 细胞衰老[1]。 Western Blot Analysis[1] Cell Line: A549 and H1299 cells Concentration: 0.3, 1 and 3 μM Incubation Time: 24, 48 and 72 h Result: Increased the expression levels of p21Cip1 and p27Kip1. Decreased the level of Skp2. Reduced the expression levels of CDK2, p-CDK2, cyclin E1, CDK4, p-CDK4 and cyclin D. Increased the levels of cleaved PARP, cleaved caspase 3, cleaved caspase 9 and Bax. Decreased the expression of PARP and Bcl-2. Cell Proliferation Assay[1] Cell Line: A549 and H1299 cells Concentration: 0.3, 1 and 3 μM Incubation Time: 24, 48 and 72 h Result: Inhibited the proliferation of A549 and H1299 cells in a dose- and time-dependent manner. The IC50 for A549 was 3 μM at 24 h, 2.5 μM at 48 h and 0.7 μM at 72 h. The IC50 for H1299 was 3.9 μM at 24 h, 1.8 μM at 48 h and 1.1 μM at 72 h. Cell Cycle Analysis[1] Cell Line: A549 and H1299 cells Concentration: 0.3, 1 and 3 μM Incubation Time: 24, 48 and 72 h Result: Arrested the cell cycle at G0/G1 in a dose- and time-dependent manner. Apoptosis Analysis[1] Cell Line: A549 and H1299 cells Concentration: 0.3, 1 and 3 μM Incubation Time: 24, 48 and 72 h Result: The ratio of JC-1 monomer/JC-1 polymer was increased in A549 and H1299 cells as the concentration was increased.
|
| In Vivo |
SCFSkp2-IN-2 (Compound AAA-237) (15 or 45 mg/kg; i.p.; daily for 14 days) 在肺癌 A549 异种移植小鼠模型中显示出抗肿瘤活性[1]。 Animal Model: A549 xenograft model[1] Dosage: 15 or 45 mg/kg Administration: Intraperitoneal administration, daily for 14 days Result: Significantly reduced tumor volume and weight. The tumor growth inhibition of the low dose and high dose was 55% and 64%, respectively. No obvious weight loss or abnormal behavior was observed. Reduced the expression of Ki67 in tumor tissue. Reduced the expression of Skp2 and Bcl-2 and increased the expression of p27, the cleaving of caspase 3, caspase 9, PARP and Bax.
|
