Synergistic anticancer effects of lipoplex-encapsulated Q7 peptide and doxorubicin against endometrial cancer cells

Endometrial cancer remains a major gynecological malignancy with a rising incidence and limited treatment options for advanced cases. Our previous study demonstrated that the Q7 anticancer peptide exerts its effects by suppressing DHCR24, regulating the AKT pathway, and inducing apoptosis in HEC-1-A endometrial cancer cells. In this study, Q7 significantly inhibits proliferation, migration, and invasion, potentially by modulating lipid metabolism and cytoskeletal remodeling pathways. Notably, Q7 transiently upregulates epithelial-mesenchymal transition (EMT)-related genes at early time points but ultimately suppresses tumor motility. To enhance its therapeutic efficacy, we encapsulated Q7 in lipoplex nanoparticles (LPPC-Q7), which exhibited superior tumor-suppressive effects both in vitro and in vivo. Furthermore, combining LPPC-Q7 with doxorubicin (LPPC-Q7-DOX) produced a synergistic effect, leading to enhanced tumor growth suppression, apoptosis induction, and inhibition of exosome production and metastasis. These findings highlight LPPC-Q7-DOX as a promising therapeutic strategy for endometrial cancer, effectively targeting lipid metabolism and cytoskeletal dynamics to combat tumor progression.