Royal jelly and doxorubicin suppressed tumor cells in the xenograft model of lung cancer via the STAT3/FOXM1/ATG7 signaling pathways in athymic nude mice: a biochemical, immunohistochemically and molecular approach.

Royal Jelly (RJ), a traditional medicinal compound with tumor-suppressive properties, was investigated for its antitumor effects on non-small cell lung cancer (NSCLC) using a mouse xenograft model. Fifty athymic nude mice were divided into five groups: a control group, an untreated NSCLC group, a doxorubicin (DOX)-treated group, an RJ-treated group, and a combined RJ + DOX treatment group. RJ was administered at 200 mg/kg/day by gavage, while DOX was given intraperitoneally at 80 mg/kg on days 10, 20, and 30. Tumor size, volume, and weight were monitored, and Kaplan-Meier analysis assessed survival. Biochemical and histopathological analyses showed that RJ modulated oxidative stress markers, reduced inflammation (IL-6, TNF-α, IL-8, interferon-γ), and inhibited tumor growth. RJ downregulated STAT3/FOXM1/ATG7 signaling pathways involved in tumor cell survival, proliferation, and metastasis. Additionally, RJ promoted mitochondrial apoptosis through increased p53 expression and reduced angiogenesis by suppressing VEGF. Immunohistochemistry revealed decreased Ki-67 expression, indicating reduced tumor cell proliferation. Molecular analyses confirmed RJ's role in modulating key apoptosis and angiogenesis pathways. When combined with DOX, RJ enhanced therapeutic efficacy, suggesting a synergistic effect. These findings highlight RJ's potential as a therapeutic agent targeting STAT3 and related pathways in NSCLC treatment, offering a promising complementary approach to conventional chemotherapy.