Triple-negative breast cancer (TNBC) has been reported to be correlated with high expression of proliferation markers as well as constitutive activation of metastasis-relevant signaling pathways. For many years, breast cancer researchers have been investigating specific and effective methods to treat or to control the development of TNBC, but promising therapeutic options remain elusive. In this study, we have demonstrated that alkylamide derivatives of bexarotene DK-1–150 and DK-1–166 induce apoptotic cell death in TNBC cell lines without causing cytotoxicity in the normal mammary epithelial cell line. Furthermore, the bexarotene derivatives also showed significant effects in inhibiting TNBC cell proliferation and migration, modulating cancer stem cell markers expressions, as well as limiting the epithelial-mesenchymal transition (EMT) activities of TNBC cell lines in terms of downregulating EMT marker and blocking nuclear translocation of β-catenin. Therefore, we propose the alkylamide derivatives of bexarotene as potential candidates for novel anticancer therapeutics against TNBC.

据报道，三阴性乳腺癌（TNBC）与增殖标志物的高表达以及与转移相关的信号通路的组成性激活有关。多年来，乳腺癌研究人员一直在研究治疗或控制TNBC发育的具体有效方法，但有希望的治疗选择仍然难以捉摸。在这项研究中，我们证明了贝沙罗汀DK-1–150和DK-1–166的烷基酰胺衍生物在TNBC细胞系中诱导凋亡性细胞死亡，而不会在正常的乳腺上皮细胞系中引起细胞毒性。此外，贝沙罗汀衍生物还显示出显着的抑制TNBC细胞增殖和迁移，调节癌症干细胞标志物表达的作用，并通过下调EMT标记和阻断β-catenin的核转运来限制TNBC细胞系的上皮-间质转化（EMT）活性。因此，我们提出贝沙罗汀的烷基酰胺衍生物作为针对TNBC的新型抗癌疗法的潜在候选药物。