The inhibition of cell death, perturbation of microtubule dynamics, and acceleration of Wnt/β-catenin/epithelial-mesenchymal transition (EMT) signaling are fundamental processes in the progression and metastasis of colorectal cancer (CRC). To explore the role of 2-stearoxyphenethyl phosphocholine (stPEPC), an alkylphospholipid-based compound, in CRC, we conducted an MTT assay, cell cycle analysis, western blot analysis, immunoprecipitation, immunofluorescence staining, Annexin V/propidium iodide double staining, small interfering RNA gene silencing, a wound-healing assay, an invasion assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in the human CRC cell lines HT29 and HCT116. stPEPC showed anti-proliferative properties and mitotic cell accumulation via upregulated phosphorylation of BUBR1 and an association between mitotic arrest deficiency 2 (MAD2) and cell division cycle protein 20 homolog (CDC20). These results suggest that activation of the mitotic checkpoint complex and tubulin polymerization occurred, resulting in mitotic catastrophe in HT29 and HCT116 cells. In addition, stPEPC attenuated cell migration and invasion by regulating proteins mediated by EMT, such as E-cadherin and occludin. stPEPC altered the protein expression of Wnt3a and phosphorylation of low-density lipoprotein receptor-related protein 6 (LRP6), glycogen synthase kinase 3β (GSK3β), and β-catenin as well as their target genes, including cMyc and cyclin D1, in CRC cells. Thus, stPEPC may be useful for developing new drugs to treat human CRC.

细胞死亡的抑制、微管动力学的扰动以及 Wnt/β-连环蛋白/上皮间质转化 (EMT) 信号传导的加速是结直肠癌 (CRC) 进展和转移的基本过程。为了探讨基于烷基磷脂的化合物 2-硬脂氧苯乙基磷酸胆碱 (stPEPC) 在 CRC 中的作用，我们进行了 MTT 测定、细胞周期分析、蛋白质印迹分析、免疫沉淀、免疫荧光染色、膜联蛋白 V/碘化丙啶双染色、小在人 CRC 细胞系 HT29 和 HCT116 中进行干扰 RNA 基因沉默、伤口愈合测定、侵袭测定和末端脱氧核苷酸转移酶 dUTP 缺口末端标记 (TUNEL) 测定。 stPEPC 通过上调 BUBR1 磷酸化以及有丝分裂停滞缺陷 2 (MAD2) 和细胞分裂周期蛋白 20 同源物 (CDC20) 之间的关联，表现出抗增殖特性和有丝分裂细胞积累。这些结果表明有丝分裂检查点复合体的激活和微管蛋白聚合的发生，导致 HT29 和 HCT116 细胞中的有丝分裂灾难。此外，stPEPC 通过调节 EMT 介导的蛋白质（例如 E-钙粘蛋白和 Occludin）来减弱细胞迁移和侵袭。 stPEPC 改变了 CRC 中 Wnt3a 的蛋白表达以及低密度脂蛋白受体相关蛋白 6 (LRP6)、糖原合酶激酶 3β (GSK3β) 和 β-连环蛋白及其靶基因（包括 cMyc 和细胞周期蛋白 D1）的磷酸化细胞。因此，stPEPC 可能有助于开发治疗人类结直肠癌的新药。