Exercise training promotes the immune cytotoxicity to enhance the inhibition of Doxorubicin in a Breast Cancer Model

Abstract Background: Physical exercise is believed to play a vital role in the prevention and treatment of cancer and its complications. However, the molecular mechanisms underlying this effect remain unclear. Methods: BALB/c female mice (n=24) were randomly divided into sedentary group (SED), exercise group (Ex), Doxorubicin group (Dox, 5 mg/kg), and Doxorubicin + exercise group (Dox + Ex) after 7 days of 4T1 cell implantation. Exercise training lasted for 28 days and included rotarod experiments and resistance training. H&E staining was used to observe histopathological changes in the tumor, spleen, and heart; The proportion of NK cells and T cells in peripheral and immune organs was analyzed by flow cytometry; The infiltration of NK and CD8 T cells and the expression levels of CD31 and VEGF in tumor tissues were evaluated by immunohistochemical; The mRNA expression levels of IL-6, IL-1β, TNF-α, TNF-α R, IFN-γ, and IFN-γ R were detected by q-PCR, and the protein expression levels of Bax, Bcl2 and cleaved caspase3 were detected by Western blot. Results: The chemotherapeutic effect of Doxorubicin on breast cancer was significantly promoted by exercise training, and its mechanism might be that exercise activates the maturation of tumor killer cells in the immune system and releases tumor suppressor factors, such as TNF-α and IFN-γ, which induces the activation of Caspase3/Bax/Bcl2 signaling pathway in tumor cells. Conclusions: It is suggested that exercise training improves chemotherapy efficacy while reducing side effects, which provides experimental evidence for the establishment of new clinical treatment strategies for breast cancer.