Preclinical and clinical studies into the bioactivity of low-dose naltrexone (LDN) for oncotherapy

Qu, Na; Meng, Yiming; Handley, Mike; Wang, Chunyan; Shan, Fengping

doi:10.1016/j.intimp.2021.107714

Cited by 8 publications

(5 citation statements)

References 128 publications

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“…Studies indicate that LDN exerts its immunoregulatory activity by binding to opioid receptors in or on tumor cells and immune cells. In the treatment of cancer and other immune-related diseases, LDN may prove to be an effective immunomodulatory agent [37].Secondly, Naloxone was administered at a concentration of 0.05 mg/Kg -1 .h -1 naloxone in this study, and the impact of other concentrations of naloxone on postoperative gastric cancer patients needs to be investigated further. Thirdly, In this study, the changes of TLR4 in gastric cancer tissues were only studied, and other proteins involved in the signal transduction pathway were not studied.…”

Section: Discussionmentioning

confidence: 99%

Effects of perioperative low-dose naloxone on the immune system in patients undergoing laparoscopic assisted total gastrectomy: a randomized controlled trial

Min,

Ma,

Leng

et al. 2024

Preprint

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Background: The low immune function after a laparoscopic total gastrectomy puts patients at risk of infection-related complications. It has been shown that low-dose naloxone (LDN) can improve the prognosis of patients suffering from chronic inflammatory diseases or autoimmune diseases. The use of LDN during perioperative procedures may reduce perioperative complications. The purpose of this study is to examine the effects of LDN on endogenous immune function in gastric cancer patients and its specific mechanisms through a randomized controlled trial. Methods: The 55 patients who underwent laparoscopic-assisted total gastrectomy were randomly assigned to either the naloxone group (n = 23) or the non-naloxone group (n = 22). The naloxone group patients would receive 0.05ug/Kg-1.h -1naloxone from 3 days before surgery to 5 days after surgery with patient controlled intravenous injection (PCIA) pump ,the non-naloxone group does not undergo special treatment. The primary outcomes were the rates of postoperative complications and immune function assessed by NK cells, CD3+ T cells, CD4+ T cells, CD8+ T cells, WBC count, Neutrophil Percentage, IL-6 and Calcitonin. The Second outcomes were assessed by the expression level of TLR4 (Toll-like receptors),IL-6 and TNF-αin gastric cancer tissue. Results: In comparison with the Non-naloxone group, the Naloxone group exhibited a lower incidence rate of infection (incision, abdomen, lungs) (P < 0.05).The number of NK cells and CD8+ T cells in the naloxone group was significantly higher than that in the Non-naloxone group at 24 hours after surgery (P < 0.05) and at 96 hours after surgery(P < 0.05),Compared with the non-naloxone group, the CD3+T cells(P < 0.05) and CD4+ T cell(P < 0.01) counts were significantly lower 24 hours after surgery. At 24 h and 96 h after surgery, the WBC count (P < 0.05) and neutrophil percentage (P < 0.05) were significantly higher in the non-naloxone group. The levels of IL-6(P < 0.05)and Calcitonin in the Non-naloxone group were significantly higher at 24 h after surgery. At 24 hours following surgery, the non-naloxone group had significantly higher levels of IL-6 (P < 0.05) and Calcitonin than the naloxone group. Compared with Naloxone group , the expression level of TLR4(P<0.05) in gastric cancer tissue in Non-naloxone group is higher; However the expression level of IL-6 (P<0.01) and TNF-α (P<0.01) in the Naloxone group is higher than that of the Non-naloxone group. Conclusion: Laparoscopic total gastrectomy patients can benefit from 0.05 ug/Kg-1. h-1 naloxone by reducing their risk of infection. Possibly, LDN alters the number of cells in the lymphocyte subpopulations, such as NK cells, CD3+T cells, CD4+T cells, and CD4/CD8+T ratios, or alters the TLR4 receptors in immune cells, thereby altering the immune cells' activity. Trial registration: The trial was registered at the Chinese Clinical Trial Registry on 24/11/2023 (ChiCTR2300077948).

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Section: Discussionmentioning

confidence: 99%

Effects of perioperative low-dose naloxone on the immune system in patients undergoing laparoscopic assisted total gastrectomy: a randomized controlled trial

Min,

Ma,

Leng

et al. 2024

Preprint

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show abstract

“…Studies indicate that LDN exerts its immunoregulatory effects by binding to opioid receptors in or on tumour cells and immune cells. In the treatment of cancer and other immune-related diseases, LDN may prove to be an effective immunomodulatory agent [ 37 ]. Second, naloxone was administered at a dosage of 0.05 mg/kg -1 .h -1 in this study, and the impact of other concentrations of naloxone on postoperative gastric cancer patients needs to be investigated further.…”

Section: Discussionmentioning

confidence: 99%

Effects of perioperative low-dose naloxone on the immune system in patients undergoing laparoscopic-assisted total gastrectomy: a randomized controlled trial

Min,

Ma,

Leng

et al. 2024

BMC Anesthesiol

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Background Low immune function after laparoscopic total gastrectomy puts patients at risk of infection-related complications. Low-dose naloxone (LDN) can improve the prognosis of patients suffering from chronic inflammatory diseases or autoimmune diseases. The use of LDN during perioperative procedures may reduce perioperative complications. The purpose of this study was to examine the effects of LDN on endogenous immune function in gastric cancer patients and its specific mechanisms through a randomized controlled trial. Methods Fifty-five patients who underwent laparoscopic-assisted total gastrectomy were randomly assigned to either a naloxone group (n = 23) or a nonnaloxone group (n = 22). Patients in the naloxone group received 0.05 µg/kg-1.h− 1naloxone from 3 days before surgery to 5 days after surgery via a patient-controlled intravenous injection (PCIA) pump, and patients in the nonnaloxone group did not receive special treatment. The primary outcomes were the rates of postoperative complications and immune function assessed by NK cell, CD3+ T cell, CD4+ T cell, CD8+ T cell, WBC count, neutrophil percentage, and IL-6 and calcitonin levels. The secondary outcomes were the expression levels of TLR4 (Toll-like receptor), IL-6 and TNF-α in gastric cancer tissue. Results Compared with the nonnaloxone group, the naloxone group exhibited a lower incidence of infection (in the incision, abdomen, and lungs) (P < 0.05). The numbers of NK cells and CD8+ T cells in the naloxone group were significantly greater than those in the nonnaloxone group at 24 h after surgery (P < 0.05) and at 96 h after surgery (P < 0.05). Compared with those in the nonnaloxone group, the CD3 + T-cell (P < 0.05) and CD4 + T-cell (P < 0.01) counts were significantly lower in the naloxone group 24 h after surgery. At 24 h and 96 h after surgery, the WBC count (P < 0.05) and neutrophil percentage (P < 0.05) were significantly greater in the nonnaloxone group. The levels of IL-6 (P < 0.05) and calcitonin in the nonnaloxone group were significantly greater at 24 h after surgery. At 24 h following surgery, the nonnaloxone group had significantly greater levels of IL-6 (P < 0.05) and calcitonin than did the naloxone group. Compared with those in the naloxone group, the expression levels of TLR4 (P < 0.05) in gastric cancer tissue in the naloxone group were greater; however, the expression levels of IL-6 (P < 0.01) and TNF-α (P < 0.01) in the naloxone group were greater than those in the nonnaloxone group. Conclusion Laparoscopic total gastrectomy patients can benefit from 0.05 ug/kg− 1. h− 1 naloxone by reducing their risk of infection. It is possible that LDN alters the number of cells in lymphocyte subpopulations, such as NK cells, CD3 + T cells, and CD4 + T cells, and the CD4+/CD8 + T-cell ratio or alters TLR4 receptor expression in immune cells, thereby altering immune cell activity. Trial registration The trial was registered at the Chinese Clinical Trial Registry on 24/11/2023 (ChiCTR2300077948).

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“…Firstly, both CBD and LDN can directly interfere with cell signalling systems within cancer cells that can result in an arrest of cell proliferation. In some circumstances, this arrest in cell cycling can lead to apoptosis (23,24). Second, both are capable of modifying the host immune system, which can re-educate and stimulate and direct an immune-based cytotoxic response against cancer cells (1,25).…”

Section: Discussionmentioning

confidence: 99%

Combination of cannabidiol with low‑dose naltrexone increases the anticancer action of chemotherapy in vitro and in vivo

et al. 2022

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We previously reported that both cannabidiol (CBD) and low-dose naltrexone (LDN) exhibit complex effects on G-protein coupled receptors, which can impact the expression and function of other members of this superfamily. These receptors feed into and interact with central signalling cascades that determine the ease by which cells engage in apoptosis, and can be used as a way to prime cancer cells to other treatments. The present study was designed to investigate the effect of combining these two agents on cancer cell lines in vitro and in a mouse model, and focused on how the sequence of administration may affect the overall action. The results showed both agents had minimal effect on cell numbers when used simultaneously; however, the combination of LDN and CBD, delivered in this specific sequence, significantly reduced the number of cells, and was superior to the regimen where the order of the agents was reversed. For example, there was a 35% reduction in cell numbers when using LDN before CBD compared to a 22% reduction when using CBD before LDN. The two agents also sensitised cells to chemotherapy as significant decreases in cell viability were observed when they were used before chemotherapy. In mouse models, the use of both agents enhanced the effect of gemcitabine, and crucially, their use resulted in no significant toxicity in the mice, which actually gained more weight compared to those without this pre-treatment (+6.5 vs. 0%). Overall, the results highlight the importance of drug sequence when using these drugs. There is also a need to translate these observations into standard chemotherapy regimens, especially for common tumour types where treatment is often not completed due to toxicities.

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Preclinical and clinical studies into the bioactivity of low-dose naltrexone (LDN) for oncotherapy

Cited by 8 publications

References 128 publications

Effects of perioperative low-dose naloxone on the immune system in patients undergoing laparoscopic assisted total gastrectomy: a randomized controlled trial

Effects of perioperative low-dose naloxone on the immune system in patients undergoing laparoscopic assisted total gastrectomy: a randomized controlled trial

Effects of perioperative low-dose naloxone on the immune system in patients undergoing laparoscopic-assisted total gastrectomy: a randomized controlled trial

Combination of cannabidiol with low‑dose naltrexone increases the anticancer action of chemotherapy in vitro and in vivo

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