Long acting propranolol and HSP-70 rich tumor lysate reduce tumor growth and enhance immune response against fibrosarcoma in Balb/c mice

• Published in: Iranian journal of immunology 2013-06, Vol.10 (2), p.70-82
• Main Authors: Khalili, Ahmad, Hassan, Zuhair Muhammad, Shahabi, Shahram, Pourfathollah, Ali Akbar, Ostad, Seyed Nasser, Noori, Shokoofe, Mahdavi, Mehdi, Haybar, Habib, Langroudi, Ladan
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Antagonists - administration & dosage; Animals; Apoptosis; Breast cancer; Cancer Vaccines - therapeutic use; Cell culture; Cell Extracts - administration & dosage; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Clinical trials; Cytokines; Cytotoxicity; Cytotoxicity, Immunologic; Female; Fibrosarcoma - immunology; Fibrosarcoma - therapy; Gastric cancer; Heat; Heat shock proteins; HSP70 Heat-Shock Proteins - administration & dosage; HSP70 Heat-Shock Proteins - immunology; Humans; Immunotherapy - methods; Interferon-gamma - metabolism; Interleukin-4 - metabolism; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Norepinephrine - antagonists & inhibitors; Ovarian cancer; Propranolol - administration & dosage; Studies; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; Tumor Burden - drug effects; Tumors
• ISSN: 1735-1383; 1735-367X

Noradrenaline (NA), the principal neurotransmitter released from sympathetic nerve terminals, influences T-cell maturation, not only directly in developing T cells, but also indirectly, by acting on the thymic nonlymphoid cells. In vitro and in vivo studies have demonstrated the anti-proliferative, anti-migratory, anti-angiogenic and cytotoxic properties of propranolol, β-AR blocker, against various cancers. To evaluate the effect of propranolol on efficacy of HSP-70 rich lysate vaccine in immunotherapy of fibrosarcoma. Mouse fibrosarcoma WEHI-164 cells were used to immunize tumor-bearing mice with or without propranolol and HSP-70. Splenocytes proliferation, cytotoxicity activity of the splenocytes, naturally occurring CD4+ CD25high T-reg cells and IFN-γ and IL-4 secretion as well as tumor size, were assessed to describe the anti-tumor immune response. A significant increase in the level of IFN-γ in the mice vaccinated with WEHI-164 cells enriched with HSP-70 and co-treated with propranolol was observed compared to controls. However, HSP enrichment or propranolol treatment alone did not enhance the immune response as measured by the level of IFN-γ. Likewise, a decrease in tumor growth in the test group (p