Series of Desloratadine Platinum(IV) Hybrids Displaying Potent Antimetastatic Competence by Inhibiting Epithelial–Mesenchymal Transition and Arousing Immune Response

Metastasis is the major obstacle
to the survival of cancer
patients.
Herein, a series of new desloratadine platinum(IV) conjugates with
promising antiproliferative and antimetastatic activities were developed
and evaluated. The candidate complex caused significant DNA damage
and stimulated mitochondrial apoptosis through the Bcl-2/Bax/caspase3
pathway. Then, it suppressed the epithelial–mesenchymal transition
(EMT) process in tumors effectively through NMT-1/HPCAL1 and β-catenin
signaling. Subsequently, the angiogenesis was inhibited with the downregulation
of key proteins HIF-1α, VEGFA, MMP-9, and CD34. Moreover, the
antitumor immunity was effectively aroused by the synergism of EMT
reversion and decrease of the histamine level; then, the macrophage
polarization from M2- to M1-type and the increase of CD4+ and CD8+ T cells were triggered simultaneously in tumors.