Abstract
Interplay between breast cancer (BC) cells and the tumor microenvironment (TME) influences the outcome of cancer treatment. Aberrant activation of signal transducer and activator of transcription 3 (STAT3) promotes the interaction and causes immunosuppression and drug resistance. Platinum(IV) complexes SPP and DPP bearing pterostilbene-derived axial ligand(s) were synthesized to inhibit the JAK2-STAT3 pathway in BC cells and regulate the TME. These complexes exerted remarkable antiproliferative activity against the triple-negative BC cells, suppressed the expression of phosphorylated STAT3 and STAT3-related cyclooxygenase-2 and IL-6, and activated caspase-3 and cleaved poly ADP-ribose polymerase, preventing the repair of DNA lesions and inducing apoptosis. Furthermore, DPP promoted the maturation and antigen presentation of dendritic cells, repressed the proliferation and differentiation of myeloid-derived suppressor cells and regulatory T cells, and facilitated the expansion of T cells. As a consequence, DPP showed excellent anticancer activity against BC with almost no general toxicity in vivo as a potential chemoimmunotherapeutic agent.
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