Abstract:Objective: To investigate the effects of Fuzheng Xiaozheng Decoction (FZXD) on the ultrastructure and telomerase reverse transcriptase (TERT) expression in different subtypes of breast cancer cells. Methods: Twelve SPF-grade female BALB/c mice (4 weeks old, 16–22 g) were acclimated for 1 week and randomized into high-, medium-, and low-dose FZXD groups and a saline group (60, 40, 20 g/kg FZXD or saline by gavage) to determine the optimal dose. A second cohort of 40 mice was randomized into FZXD alone, paclitaxel (PTX) alone, FZXD+PTX combination, and blank control groups (n=10 each). FZXD was given at 60 g/kg twice daily, PTX injected intraperitoneally at 10 mg/kg twice weekly, and the combination group received both regimens for 7 days. One hour after the last dose, blood was collected, serum separated, heat-inactivated, and sterile-filtered (0.22 μm). Drug-containing serum was used to treat breast cancer cells. Cell proliferation (CCK-8), ultrastructure (TEM), TERT mRNA (RT-qPCR), TERT protein (Western blot), and telomere length (RT-qPCR, T/S ratio) were assessed. Results: High-dose FZXD-medicated serum reduced breast cancer cell viability below 50% at 48 h. TEM showed swollen mitochondria with ruptured outer membranes, disordered cristae, cytoplasmic vacuolization, and disrupted plasma membranes in FZXD, PTX, and combination groups. All treatment groups exhibited reduced TERT mRNA/protein levels and shortened telomeres vs. control. Conclusion: Fuzheng Xiaozheng Decoction suppresses breast cancer progression by downregulating TERT expression.