Combination of Propranolol and Heated 4T1 Cells Elicits Beneficial Response Against Mouse Model of Breast Cancer

Abstract

Background: Induction of Th1 responses against tumor antigens may be a useful strategy to control malignancy. In this respect, previous studies have shown that beta-adrenoreceptor antagonists can promote cellular immune responses. Objectives: This survey was done to evaluate the beneficiary of a new immunotherapy method against breast cancer made by mixing heated 4T1 cells and propranolol, as an adjuvant. Methods: Subcutaneously injected live 4T1 cells (1 × 104) were used to induce breast cancer in six to eight-week-old female Balb/c mice. when all mice had a palpable tumor, immunotherapy was dawned. Mice in the treatment groups were vaccinated, twice at a one-week interval, with the extract of heated 4T1(1 × 105) either alone or in combination with propranolol (6 mg/kg). Negative control mice received phosphate-buffered saline (PBS) as the same schedule. One-half of the mice were euthanized one week after the last vaccination to investigate the immune response profile. Other animals were kept until death occurred spontaneously. Results: Combined immunotherapy with propranolol and extract of heated 4T1 had synergistic effects, causing a more desirable survival curve and slower tumor growth when compared to other tumor-bearing mice receiving only heated 4T1 or PBS. Furthermore, combined immunotherapy significantly augmented the production of IFN-γ nitric oxide production, respiratory burst, and cytotoxicity of natural killer cells in the splenocyte culture of tumor-bearing mice. Conversely, combined immunotherapy significantly regressed the production of TGF-β and IL-10 in the splenocyte population compared to cytokine production by splenocytes from other groups. Conclusions: Combined heated 4T1 cells with propranolol promote beneficial outcomes in the animal model of breast cancer.