Panax notoginseng improves the sensitivity of non-small cell lung cancer to cisplatin by inhibiting Akt signaling.

Abstract

BackgroundCisplatin (DDP) resistance is a major challenge in the management of non-small cell lung cancer (NSCLC). Panax notoginseng has anticancer effects on a variety of solid tumors, but data on NSCLC and DDP resistance are lacking.ObjectiveTo investigate the effect of Panax notoginseng on DDP resistance in NSCLC in vitro and in vivo and explore the mechanisms involved.MethodsA 1 g/mL Panax notoginseng extract was prepared to treat the A549 and DDP-resistant A549/DDP cell lines. Cell proliferation was assessed using the CCK-8 assay, and apoptosis was measured via Annexin V-FITC/PI staining and flow cytometry. Glucose uptake, ATP production, and lactate levels were evaluated. Protein levels of p-AKT, GLUT1, HKII, and cleaved-caspase-3 were analyzed by Western blot. IGF1 was used to activate the Akt pathway. In vivo, A549/DDP cells were inoculated into nude mice to establish subcutaneous tumors, and tumor growth and apoptosis were assessed.ResultsPanax notoginseng inhibited A549/DDP cell proliferation, enhanced DDP-induced apoptosis, and reduced glucose uptake, ATP, and lactate levels (all p < 0.05). Combined treatment decreased p-AKT, GLUT1, and HKII expression while increasing cleaved-caspase-3(p < 0.05). IGF1 reversed these effects, indicating Akt pathway involvement (p < 0.05). In vivo, Panax notoginseng and DDP significantly suppressed tumor growth and increased apoptosis in tumors, confirming enhanced chemosensitivity (p < 0.05).ConclusionPanax notoginseng can improve the sensitivity of A549/DDP cells to DDP by inhibiting the effects of TRIM46 and Akt signaling pathways on glycolysis in vivo and in vitro.