Lycorine suppresses cell growth and attenuates stemness through PI3K/AKT pathway in ovarian cancer

Ovarian cancer remains the most lethal gynecological malignancy worldwide, with poor prognosis due to chemotherapy resistance and cancer stem cell-driven recurrence. This study comprehensively investigates the antitumor effects of lycorine, a natural alkaloid derived from Lycoris radiata, on human ovarian cancer models. Our results demonstrate that lycorine significantly inhibits ovarian cancer cell proliferation, induces apoptosis, and suppresses cancer stemness properties through modulation of the PI3K/AKT signaling pathway. In vitro, lycorine treatment reduced the expression of stemness markers (CD133, CD44, NANOG, SOX2, OCT4, and LIN28) and impaired tumor sphere formation. RNA sequencing and pathway enrichment analysis confirmed significant inhibition of PI3K/AKT signaling, accompanied by decreased phosphorylation of AKT and mTOR. In vivo, lycorine (5 mg/kg) effectively suppressed tumor growth in A2780-luc xenograft models, reduced stem cell subpopulations, and exhibited minimal toxicity. Furthermore, lycorine sensitized ovarian cancer cells to cisplatin and counteracted cisplatin-induced enrichment of cancer stem cells. These findings highlight lycorine as a promising multi-target therapeutic agent against ovarian cancer, particularly for addressing stemness-driven chemoresistance and recurrence.