Naloxone can improve the anti-tumor immunity by reducing the CD4+CD25+Foxp3+ regulatory T cells in BALB/c mice

Hassan, Agheel Tabar Molla; Hassan, Zuhair Mohammad; Moazzeni, Seyed Mohammad; Mostafaie, Ali; Shahabi, Shahram; Ebtekar, Massoumeh; Hashemi, Seyed Mahmoud

doi:10.1016/j.intimp.2009.08.008

Cited by 23 publications

(9 citation statements)

References 30 publications

(37 reference statements)

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“…In the present investigation, although the administration of NLX and NLX/IFA with rPvAMA‐1 induced significantly higher levels of IFN‐γ production than in the control groups, still a significant level of IgG1 and IgG2b was detected. These results suggest that the administration of NLX in combination with rPvAMA‐1 increased the ability of this formulation to induce a mixed Th1/Th2 immune response, which was in contrast to previous published works .…”

Section: Discussioncontrasting

confidence: 99%

Administration of naloxone in combination with recombinant Plasmodium vivax AMA‐1 in BALB/c mice induces mixed Th1/Th2 immune responses

Someabozorg

Mirkazemi

Mehrizi

et al. 2015

Parasite Immunology

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Naloxone (NLX) has the ability to shift the immune response to a Th1 profile. Therefore, the adjuvant efficacy of NLX with recombinant P. vivax apical membrane antigen-1(rPvAMA-1) in BALB/c mice was evaluated. Mice were immunized subcutaneously with purified rPvAMA-1 formulated with NLX (doses of 5 mg/kg body weight) alone or in combination with IFA. A significant increase in anti-PvAMA-1 IgG antibody after the second boost (mean OD = 2·08 and 2·17, in groups received, rPvAMA-1/NLX and rPvAMA-1/NLX/IFA, respectively) was detected. IgG1 and IgG2b were the predominant isotypes in all immunized mouse groups. In immunized mice with rPvAMA-1/NLX (mean: 1036 pg/mL) and with rPvAMA-1/NLX/IFA (mean: 1024 pg/mL), IFN-γ was elicited in response to rPvAMA-1 after the second boost. No detectable IL-4 secretion was determined in all tested groups. In conclusion, the administration of NLX alone or NLX/IFA with rPvAMA-1 in BALB/c mice, which induced mixed Th1/Th2 immune responses, was comparable with that of the same recombinant antigen with CFA/IFA adjuvant. The results indicate that NLX alone may possibly not be considered as a potent Th1 adjuvant in PvAMA-1-based vaccine. However, in order to modulate immune responses from mixed Th1/Th2 to strong and protective Th1 response, further study is warranted on combination of NLX with other adjuvants such as CpG motifs or MPL in proper vaccine formulation. Additionally, dose-response study is necessary to determine the effect of different doses of antigen combined with NLX (at various doses) in Balb/c mice.

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Section: Discussioncontrasting

confidence: 99%

Administration of naloxone in combination with recombinant Plasmodium vivax AMA‐1 in BALB/c mice induces mixed Th1/Th2 immune responses

Someabozorg

Mirkazemi

Mehrizi

et al. 2015

Parasite Immunology

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“…It has been reported that naloxone has multiple activities in numerous processes. It acts as an immunoadjuvant in cancer immunotherapy, 1 – 3 and it regulates, in conjunction with other opioids, the apoptosis 4 – 6 in human cancer cells. 7 , 8 In addition, it has been proved that naloxone can influence the proliferation and neurogenesis in cultured rat adult hippocampal progenitors.…”

Section: Introductionmentioning

confidence: 99%

The effects of naloxone on human breast cancer progression: in vitro and in vivo studies on MDA.MB231 cells

Bimonte

Barbieri

Cascella

et al. 2018

OTT

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BackgroundNaloxone is viewed as a specific competitive opioid antagonist acting at the level of opioid receptors (μ, δ, and κ) with blended agonist-adversary or agonist action. The role of naloxone in tumor cell growth has been poorly studied in human cancer cell lines.Materials and methodsIn the present study, we report findings from in vitro and in vivo experiments performed to evaluate the effects of naloxone on human breast cancer cell growth and progression. In vitro assays were conducted on estrogen receptor-negative human breast carcinoma cells, MDA.MB231, treated with naloxone at different concentrations (10–100 μM). In vivo experiments were performed on a mouse model of human triple-negative breast cancer generated by using MDA.MB231 injected subcutaneously in mice. Naloxone was daily intraperitoneally injected in mice at 0.357 mg/kg for 2 weeks and at 0.714 mg/kg for the next 2 weeks. Microvessels formation was detected by fluorescein isothiocyanate-dextran (100 μL) injected into the tail vein of mice and confirmed by immunohistochemistry with CD31 on mice tumor sections.ResultsIn vitro tests showed that the cell proliferation of MDA.MB231 was inhibited by naloxone in a dose-dependent manner, whereas the cell death was increased. In vivo studies demonstrated that tumors of mice treated with naloxone were significantly smaller than those observed in the control groups, as long as naloxone was administered. Finally, naloxone was not able to impair the microvessel formation in tumors of treated mice.ConclusionOur data showed, for the first time, that naloxone reduced breast cancer progression without affecting angiogenesis.

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“…The combined heated 4T1 cells and NLX significantly increased splenocytes' proliferative response, more so than that observed after treatment with heated 4T1 cells. In this regard, previous reports showed that the opioid possesses an antiproliferative effect on T-cells, and, in contrast, naloxone accelerates the mitogen-induced splenocyte proliferation (10,37,38).…”

Section: Discussionmentioning

confidence: 90%

“…Tumors are able to evade immunity by secreting some mediators like TGF-β and IL-10. TGF-β and IL-10 tend to inhibit the proliferation and activation of lymphocytes and macrophages and consequently suppress cell-mediated immunity, and they are required to control tumor growth (37,39). Both cytokines can induce the development of regulatory T cells, which have been found in a variety of tumors, and may suppress T cell responses to tumors.…”

Section: Discussionmentioning

confidence: 99%

Combination immunotherapy with extract of heated 4T1 and naloxone in mouse model of breast cancer

Jahangiri¹,

Froushani²,

Delirezh³

2016

Turk J Med Sci

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Naloxone can improve the anti-tumor immunity by reducing the CD4+CD25+Foxp3+ regulatory T cells in BALB/c mice

Cited by 23 publications

References 30 publications

Administration of naloxone in combination with recombinant Plasmodium vivax AMA‐1 in BALB/c mice induces mixed Th1/Th2 immune responses

Administration of naloxone in combination with recombinant Plasmodium vivax AMA‐1 in BALB/c mice induces mixed Th1/Th2 immune responses

The effects of naloxone on human breast cancer progression: in vitro and in vivo studies on MDA.MB231 cells

Combination immunotherapy with extract of heated 4T1 and naloxone in mouse model of breast cancer

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