Objective  This study aimed to observe the synergistic effect of a new tumor vaccine combined with metronomic chemotherapy in vivo on breast cancer. This study was also conducted to investigate the mechanism of this combination.

  Methods  Balb/cmice inoculated with 4T1 mouse breast cancer cell were used as tumor models. High-mobility group nucleosome-binding protein 1 (HMGN1) gene was used to transfect 4T1 cell lines as cancer vaccines. After 4T1 cell was inoculated, the mice were randomized into four groups: normal saline (NS); metronomic gemcitabine (GEM) alone; cancer vaccine alone; and combination therapy group. Tumor growth and potential toxicities of these regimens were observed. The Foxp3 expression of regulatory T cells (Tregs) was detected by western blot and immunohistochemical staining. The microvessel density (MVD) of the tumor was also detected by immunohistochemical staining.

  Results  The tumor volume of the mice was significantly lower in the combination group than in the MET group or cancer vaccine group (P < 0.05). This result exhibited a higher significant difference than the tumor volume of the mice in the NS group (P < 0.01). Foxp3 expression was significantly lower in the mice treated with GEM (combination or MET group). MVD was significantly lower in these two groups than in the cancer vaccine group or NS group (P < 0.05). Furthermore, adverse reactions slightly occurred in each group.

  Results  Conclusion: The combination of cancer vaccines and metronomic GEM is a very active and well-tolerated regimen for breast cancer in mice.