Synergistic anticancer effects of liposomal doxorubicin and aprepitant combination therapy in breast cancer: Preclinical insights and therapeutic potential

Doxil (PEGylated Liposomal Doxorubicin) is a formulation of doxorubicin encapsulated in pegylated liposomes, which prolongs its presence in the bloodstream, enhancing drug delivery to cancer cells. This study investigates the synergistic anticancer effects of Doxil combined with aprepitant, a neurokinin-1 receptor antagonist, in breast cancer (BC) through laboratory and animal experiments. Cytotoxicity was assessed using the MTT method, while mRNA and protein expression were evaluated via qRT-PCR and Western blot. Flow cytometry was employed to analyze cell cycle and apoptosis distribution. Additionally, cell migration and angiogenesis were examined using wound-healing and CAM assays, respectively. The combined therapy significantly enhanced apoptosis and antiproliferation, as indicated by increased apoptotic and necrotic cell populations, G2/M phase cell accumulation, and changes in key cell cycle (cyclin D1, p53) and apoptosis (Bcl-2 and Bax) markers. In a murine BC model, Doxil and aprepitant treatment notably reduced tumor size. Furthermore, the combination therapy exhibited significant antimetastatic and antiangiogenic effects, characterized by decreased cell migration, altered MMP-2, MMP-9, VEGFA, and VEGFR1 levels, and reduced vasculature in CAM assays. These results suggest the potential of Doxil and aprepitant as a promising therapeutic approach for BC, meriting further clinical investigation.