Abstract
In the present study, the immunomodulatory and synergistic anti-tumor activity of thymosin α1-thymopentin fusion peptide (Tα1-TP5) was investigated in vivo. In addition, the potential receptor of Tα1-TP5 was investigated by surface plasmon resonance (SPR) binding studies. It was found that Tα1-TP5 (305 μg/kg) alleviated immunosuppression induced by hydrocortisone (HC). Tα1-TP5 (305 μg/kg) combined with cyclophosphamide (CY) had a better tumor growth inhibitory effect than CY alone. Furthermore, Tα1-TP5 had a higher affinity (KD=6.84 μmol/L) to toll-like receptor 2 (TLR2) than Tα1 (K(D)=35.4 μmol/L), but its affinity was not significantly different from that of TP5. The results of our present work indicate that Tα1-TP5 can possibly be developed as a new immunomodulatory agent.
Keywords:
Immunoregulatory activity; Surface plasmon resonance; Synergistic anti-tumor activity; Thymosin α1–thymopentin; Toll-like receptor 2.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
MeSH terms
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Animals
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Antineoplastic Agents / immunology
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents, Alkylating / pharmacology
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Atrophy
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B7-2 Antigen / metabolism
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Cyclophosphamide / pharmacology
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Drug Synergism
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Histocompatibility Antigens Class I / metabolism
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Hydrocortisone / pharmacology
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Immunologic Factors / metabolism
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Immunologic Factors / pharmacology*
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Immunosuppressive Agents / pharmacology
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Interferon-gamma / blood
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Male
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Melanoma, Experimental / drug therapy*
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Melanoma, Experimental / immunology
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Melanoma, Experimental / pathology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Protein Binding
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Skin Neoplasms / drug therapy*
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Skin Neoplasms / immunology
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Skin Neoplasms / pathology
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Surface Plasmon Resonance
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Thymalfasin
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Thymocytes / drug effects
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Thymocytes / immunology
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Thymocytes / pathology
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Thymopentin / immunology
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Thymopentin / metabolism
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Thymopentin / pharmacology*
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Thymosin / analogs & derivatives*
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Thymosin / immunology
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Thymosin / metabolism
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Thymosin / pharmacology
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Thymus Gland / drug effects
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Thymus Gland / immunology
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Thymus Gland / pathology
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Time Factors
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Toll-Like Receptor 2 / metabolism*
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Tumor Burden / drug effects
Substances
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Antineoplastic Agents
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Antineoplastic Agents, Alkylating
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B7-2 Antigen
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Cd86 protein, mouse
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Histocompatibility Antigens Class I
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Immunologic Factors
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Immunosuppressive Agents
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Tlr2 protein, mouse
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Toll-Like Receptor 2
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Thymosin
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Interferon-gamma
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Cyclophosphamide
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Thymopentin
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Thymalfasin
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Hydrocortisone