Synergistic effects of anlotinib and DDP synergy in breast cancer treatment: inhibiting of cell growth and migration, and augmenting apoptosis and autophagy via modulation of the VEGF/JAK2/STAT3 axis

Abstract

Abstract Anlotinib has been shown to have good anti-tumor effects in a variety of tumors, including breast cancer (BRCA); however, the combined anti-tumor efficacy of anlotinib and DDP in BRCA, as well as the underlying mechanism, remain to fully elucidated. This study aims to explore the role of VEGFA expression in BRCA and the therapeutic efficacy of anlotinib, alone and in combination with cisplatin (DDP), in treating BRCA. BRCA cells were treated with or without anlotinib and/or DDP. The proliferation, migration and invasion capabilities of BRCA cells were evaluated using CCK-8 assays, clone formation assays, wound healing assays and transwell assays. Cell apoptosis was detected by Hoechst33342 fluorescence staining and flow cytometry technique. The potential mechanism of anlotinib in the development of BRCA was predicted through bioinformatics analysis, and the mRNA or protein levels were subsequently quantified using qPCR and western blot. The anti-breast cancer efficacy of anlotinib was evaluated in vivo using a xenograft tumor model. Our findings reveal that increased VEGFA expression in BRCA patients is associated with a poorer prognosis, underscoring the need for targeted therapeutic strategies. We demonstrate that both anlotinib and DDP independently inhibit BRCA cell growth, migration, and invasion. Their combination exhibits a synergistic effect, significantly enhancing the inhibition of these oncogenic processes. This synergy is further evident in the induction of apoptosis and autophagy within BRCA cells. Mechanistically, anlotinib's effectiveness is attributed to its inhibition of the JAK2/STAT3 pathway, a critical axis in BRCA progression. In vivo studies reinforce these findings, anlotinib markedly inhibits tumor growth in mice xenografted. This study confirms the efficacy of anlotinib or in combination with DDP and elucidates the mechanism behind anlotinib's effectiveness, highlighting its role in inhibiting the JAK2/STAT3 pathway. These findings pave the way for further clinical exploration and development of anlotinib-based therapies, offering hope for improved outcomes in breast cancer management.