Triple-negative breast cancer (TNBC) stands for a refractory subtype, which predicts poor prognosis and has no effective therapies yet for improving it. Given the restrictions of traditional treatments, novel therapeutic strategies need excavating to alleviate the intrinsic or acquired resistance. Ribociclib, a selective CDK4/6 inhibitor, has successfully prevented cancers from deteriorating by intervening the CDK4/6-cyclin D-Rb-E2F pathway, especially for estrogen receptor-positive (ER +) breast cancer. However, there still remains limited accessibility referring to TNBC. Performing experiments on MDA-MB-231 cells, we found that LEE011 could suppress cell proliferation, and this suppression tended to be dose-dependently. Western blotting analysis presented significant decrease with the expression of CDK4/6 after LEE011 treated, and other proteins associated with this axis such as cyclin D1, p-Rb, Rb, E2F1 showed aberrant changes. Moreover, LEE011 induced G0-G1 phase cell cycle arrest, promoted cell apoptosis, and reduced cell migration in vitro. In addition, tumor growth was remarkably impeded without obvious side-effects in MDA-MB-231 xenograft models. Our research has identified that LEE011 was not completely invalid for MDA-MB-231. Considering its pivotal status in TNBC, the CDK4/6-cyclin D-Rb-E2F pathway informed us the possibility and practicality of Ribociclib (LEE011) as pharmacological intervention, but challenges warrant further validation in prospective studies.

中文翻译：

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Ribociclib（LEE011）通过抑制CDK4 / 6-cyclin D-Rb-E2F途径抑制细胞增殖并诱导MDA-MB-231凋亡。

三阴性乳腺癌（TNBC）代表难治性亚型，预后不良，尚无有效的治疗方法可改善其。考虑到传统疗法的局限性，需要挖掘新的治疗策略以减轻内在或获得性耐药。Ribociclib是一种选择性CDK4 / 6抑制剂，已通过干预CDK4 / 6-cyclin D-Rb-E2F途径成功预防了癌症恶化，尤其是对于雌激素受体阳性（ER +）乳腺癌。但是，仍然存在关于TNBC的有限可访问性。在MDA-MB-231细胞上进行的实验，我们发现LEE011可以抑制细胞增殖，并且这种抑制作用是剂量依赖性的。Western blotting分析显示，LEE​​011处理后CDK4 / 6的表达显着降低，其他与此轴相关的蛋白质，例如细胞周期蛋白D1，p-Rb，Rb，E2F1则显示出异常的变化。此外，LEE011诱导G0-G1期细胞周期停滞，促进细胞凋亡，并减少体外细胞迁移。另外，在MDA-MB-231异种移植模型中，没有明显的副作用，肿瘤生长受到显着阻碍。我们的研究发现，LEE011对于MDA-MB-231并非完全无效。考虑到其在TNBC中的关键地位，CDK4 / 6-cyclin D-Rb-E2F途径为我们提供了Ribociclib（LEE011）作为药理学干预的可能性和实用性，但挑战需要在前瞻性研究中进一步验证。另外，在MDA-MB-231异种移植模型中，没有明显的副作用，肿瘤生长受到显着阻碍。我们的研究发现，LEE011对于MDA-MB-231并非完全无效。考虑到其在TNBC中的关键地位，CDK4 / 6-cyclin D-Rb-E2F途径为我们提供了Ribociclib（LEE011）作为药理学干预的可能性和实用性，但挑战需要在前瞻性研究中进一步验证。另外，在MDA-MB-231异种移植模型中，没有明显的副作用，肿瘤生长受到显着阻碍。我们的研究发现，LEE011对于MDA-MB-231并非完全无效。考虑到其在TNBC中的关键地位，CDK4 / 6-cyclin D-Rb-E2F途径为我们提供了Ribociclib（LEE011）作为药理学干预的可能性和实用性，但挑战需要在前瞻性研究中进一步验证。