Abstract: Background and purpose: There is severe immune imbalance in breast cancer patients. Thymosin α1 (Tα1) acts as an immune enhancer. The aim of this study was to explore the effects of docetaxel (DCT) combined with Tα1 on number of regulatory T cell (Treg) in immune microenvironment of rats with breast cancer, and preliminarily analyze its action mechanism. Methods: Sixty female SD rats were randomly divided into model group, DCT group (10 mg/kg), Tα1 group (0.8 mg/kg) and three DCT+Tα1 (10 mg/kg DCT; 0.2, 0.4, 0.8 mg/kg Tα1) groups with 10 cases in each group. SD female rats were inoculated with breast cancer cell line SHZ-88 to construct xenograft models. After tumor formation, DCT group, Tα1 group and DCT+Tα1 group were given intraperitoneal injection of DCT and Tα1 respectively. The administration period was 20 d, once a day. The tumor volume was measured. TdT-mediated dUTP nick end labeling (TUNEL) staining was applied to detect apoptosis of tumor cells. The number of CD4 ⁺ CD25 ⁺ Foxp3 ⁺ Treg, expression of programmed death-1 (PD-1) and number of Treg in tumor tissues were detected by flow cytometry. The expressions of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) in tumor tissues were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of PD-1 and programmed death ligand-1 (PD-L1) in tumor tissues were detected by Western blot. Results: Compared with model group, drug administration effectively inhibited tumor growth, promoted apoptosis of tumor cells and significantly down-regulated the number of CD4 ⁺ CD25 ⁺ Foxp3 ⁺ Treg and expressions of IL-10, TGF-β, PD-1 and PD-L1 (P ＜ 0.05). The action effect in DCT+0.8 mg/kg Tα1 group was the most significant, which was significantly better compared with the other administration groups. Conclusion: DCT combined with Tα1 can inhibit growth of rat tumor. The effect of DCT+0.8 mg/kg Tα1 is the most significant, and its mechanism may involve down-regulating expression of PD-1/PD-L1 and inhibiting infiltration of CD4 ⁺ CD25 ⁺ Foxp3 ⁺ Treg.

Key words:  Docetaxel, Thymosin α1, Breast cancer, Immunity, Regulatory T cell