Modulation of breast cancer progression in high-altitude hypoxia by Tongqiaohuoxue Decoction via HIF-1α/VEGF signaling

To explore the therapeutic efficacy and underlying mechanisms of Tongqiao Huoxue Decoction (THD) in the context of breast cancer development under high-altitude hypoxic conditions. We established an in vivo breast cancer hypoxia model and utilized a small animal in vivo imaging system for oncological investigation. Routine blood tests and coagulation profile tests were conducted to assess platelet count and coagulation function. Pathological changes in tumor tissues were observed. Immunohistochemistry (IHC) was employed to detect positive rates of hypoxia inducible factor (HIF)-1α, P-selectin (CD62P), platelet-derived growth factor receptor (PDGFR), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (BFGF) in tumor tissues. Western blotting was used to evaluate protein expression levels of HIF-1α, VEGF, cellular myelocytomatosis oncogene (c-MYC), and platelet-derived growth factor receptor β (PDGFR-β). Under hypoxic conditions, orthotopic tumor volume and weight, and the number and area of lung metastases significantly increased. Platelet count increased, and prothrombin time was prolonged. IHC and immunoblot analyses revealed that HIF-1α, VEGF, and PDGFR-β expression were upregulated under hypoxia. Following THD treatment, the volume and weight of orthotopic tumors decreased, and so did the number and area percentage of lung metastases. Platelet and D-dimer counts decreased, while activated partial thromboplastin time and thrombin time were prolonged. Protein expression levels of HIF-1α, VEGF, c-MYC, and PDGFR-β were downregulated. Based on the current data, the ameliorative effects of THD on tumor hypoxia and hypercoagulability under high-altitude conditions may be associated with the modulation of the HIF-1α/VEGF signaling pathway, providing clues to its potential mechanisms for suppressing tumor growth, metastasis, and angiogenesis.