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.
Keywords: Triple-negative breast cancer; apoptosis; cell cycle; proliferation; ribociclib (LEE011).