Qing Cheng; Ting Yang & Conghua Chen

The renin–angiotensin (RA) system has been linked to lung cancer development, yet detailed mechanistic insights remain limited. Bergenin, a traditional medicinal compound with demonstrated anti-tumor properties, was evaluated for its effects on non- small cell lung cancer (NSCLC) using a mouse xenograft model. Fifty athymic nude mice were allocated into five groups: a control group, an untreated NSCLC group, a doxorubicin (DOX)–treated group, a Bergenin-treated group, and a Bergenin plus DOX combination group. Bergenin was administered orally at 50 mg/kg/day, while DOX was delivered intraperitoneally at 50 mg/kg on days 10, 20, and 30. Tumor growth was tracked by measuring size, volume, and weight, and survival was analyzed with Kaplan–Meier estimates. Biochemical and histopathological assessments showed that Bergenin modulated oxidative stress markers, attenuated inflammatory mediators (IL-6, TNF-α, IL-8, Ang II, IFN-γ), and impeded tumor progression. The treatment downregulated signaling pathways associated with tumor cell survival, proliferation, and metastasis, including nAChR/Src/STAT3 and IGF-1R. Immunohistochemical analysis demonstrated reduced AGT expression, consistent with diminished tumor cell proliferation. Molecular investigations supported Bergenin’s influence on critical apoptosis and angiogenesis pathways. In combination with DOX, Bergenin amplified therapeutic efficacy, indicating a potential synergistic interaction. Our results suggest that Bergenin may serve as a therapeutic agent targeting nAChR/Src/STAT3 and IGF-1R/Akt related signaling cascades in NSCLC, providing a promising complementary strategy to standard chemotherapy.

KEY WORDS: Bergenin; nAChR/Src/STAT3; Doxorubicin; Lung cancer; A549 cells. INTRODUCTION

CHENG, Q.; YANG, T. & CHEN, C. The anticancer action of Bergenin in NNK-induced pulmonary cancer: Mechanisms involving nAChR/ Src/STAT3 activation of the renin-angiotensin system and IGF-1R signaling. Int. J. Morphol., 44(3):934-948, 2026.