Tropisetron attenuates tumor growth and progression in an experimental model of mouse lung cancer

Rashidi, Mohsen; Bazi, Ali; Shiran, Mohammad Reza; Bagheri, Abouzar; Mehrabadi, Abbas Rezaeian; Kalantar, Hadi; Ghafouri, Zahra; Hosseini, Sayed Mostafa

doi:10.1002/jcb.29395

Cited by 15 publications

(8 citation statements)

References 67 publications

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“…In addition, the polymorphisms of IL-4R involved in the etiology of pancreatic cancer have been examined [104]. Consequently, increased levels of protein and mRNA of the IL-4/IL-13-receptor axis may be useful biomarkers for disease activity and prognosis in patients with pancreatic cancer [123][124][125].…”

Section: Future Directions Of Researchmentioning

confidence: 99%

Involvement of IL-4, IL-13 and Their Receptors in Pancreatic Cancer

Shi

Song

Traub

et al. 2021

IJMS

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Interleukin (IL)-4 and IL-13 are known as pleiotropic Th2 cytokines with a wide range of biological properties and functions especially in immune responses. In addition, increasing activities have also been determined in oncogenesis and tumor progression of several malignancies. It is now generally accepted that IL-4 and IL-13 can exert effects on epithelial tumor cells through corresponding receptors. Type II IL-4 receptor (IL-4Rα/IL-13Rα1), predominantly expressed in non-hematopoietic cells, is identified to be the main target for both IL-4 and IL-13 in tumors. Moreover, IL-13 can also signal by binding to the IL-13Rα2 receptor. Structural similarity due to the use of the same receptor complex generated in response to IL-4/IL-13 results in overlapping but also distinct signaling pathways and functions. The aim of this review was to summarize knowledge about IL-4 and IL-13 and their receptors in pancreatic cancer in order understand the implication of IL-4 and IL-13 and their receptors for pancreatic tumorigenesis and progression and for developing possible new diagnostic and therapeutic targets.

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Section: Future Directions Of Researchmentioning

confidence: 99%

Involvement of IL-4, IL-13 and Their Receptors in Pancreatic Cancer

Shi

Song

Traub

et al. 2021

IJMS

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“… 149 Subsequently, the antineoplastic activities of 5‐HTR3 antagonists were confirmed and deciphered in both in vitro studies and mouse models of lung cancer. 148 , 149 …”

Section: Therapeutic Potential Of Serotonergic Pathway In Cancermentioning

confidence: 99%

“…149 Subsequently, the antineoplastic activities of 5-HTR3 antagonists were confirmed and deciphered in both in vitro studies and mouse models of lung cancer. 148,149 However, an FDA-approved HTR4 agonist called Tegaserod, which is typically employed in treating irritable bowel syndrome, has been found to effectively induce apoptosis in both BRAF V600E and BRAF WT melanoma. Tegaserod inhibited PI3K-AKT-mTOR signalling and synergistically enhanced the effects of a standard treatment, Vemurafenib, in human melanoma cell lines.…”

Section: -Ht Receptor-directed Therapymentioning

confidence: 99%

Serotonin signalling in cancer: Emerging mechanisms and therapeutic opportunities

Chen,

Huang,

et al. 2024

Clinical & Translational Med

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BackgroundSerotonin (5‐hydroxytryptamine) is a multifunctional bioamine serving as a neurotransmitter, peripheral hormone and mitogen in the vertebrate system. It has pleiotropic activities in central nervous system and gastrointestinal function via an orchestrated action of serotonergic elements, particularly serotonin receptor‐mediated signalling cascades. The mitogenic properties of serotonin have garnered recognition for years and have been exploited for repurposing serotonergic‐targeted drugs in cancer therapy. However, emerging conflicting findings necessitate a more comprehensive elucidation of serotonin's role in cancer pathogenesis.Main body and conclusionHere, we provide an overview of the biosynthesis, metabolism and action modes of serotonin. We summarise our current knowledge regarding the effects of the peripheral serotonergic system on tumourigenesis, with a specific emphasis on its immunomodulatory activities in human cancers. We also discuss the dual roles of serotonin in tumour pathogenesis and elucidate the potential of serotonergic drugs, some of which display favourable safety profiles and impressive efficacy in clinical trials, as a promising avenue in cancer treatment.Key points Primary synthesis and metabolic routes of peripheral 5‐hydroxytryptamine in the gastrointestinal tract. Advanced research has established a strong association between the serotonergic components and carcinogenic mechanisms. The interplay between serotonergic signalling and the immune system within the tumour microenvironment orchestrates antitumour immune responses. Serotonergic‐targeted drugs offer valuable clinical options for cancer therapy.

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“…Tropisetron is a 5‐HT 3 receptor antagonist. It has been shown to attenuate the growth and progression of tumours in an experimental model of lung cancer in mice 29 . In addition, a 5‐HT 3 receptor antagonist, as an anti‐emetic drug, may also decrease lung injury and inflammation of the airway mucosa by reducing regurgitation of digestive secretions into the trachea caused by nausea and vomiting.…”

Section: Introductionmentioning

confidence: 99%

“…It has been shown to attenuate the growth and progression of tumours in an experimental model of lung cancer in mice. 29 In addition, a 5-HT 3 receptor antagonist, as an anti-emetic drug, may also decrease lung injury and inflammation of the airway mucosa by reducing regurgitation of digestive secretions into the trachea caused by nausea and vomiting. Therefore, use of a 5-HT 3 receptor antagonist before mechanical ventilation may reduce the mortality risk of ventilated patients in the ICU.…”

mentioning

confidence: 99%

Mediators of neutrophil–lymphocyte ratio in the relationship between ondansetron pre‐treatment and the mortality of ICU patients on mechanical ventilation: Causal mediation analysis from the MIMIC‐IV database

Zhou

Tao

Zhang

et al. 2022

Brit J Clinical Pharma

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Aims The mortality of critically ill patients undergoing mechanical ventilation (MV) is high and few strategies are available. We explored the relationship between ondansetron pre‐treatment, the neutrophil–lymphocyte ratio (NLR), and platelet–lymphocyte ratio (PLR), and mortality of ventilated patients in the intensive care unit. Methods We developed a retrospective cohort study that involved patients undergoing MV in the Multiparameter Intelligent Monitoring in Intensive Care IV (MIMIC‐IV) database. Causal mediation analysis was conducted to assess the relationship of ondansetron use and mortality and to explore the potential causal pathway mediated by the NLR or PLR. The primary outcome was 28‐day mortality. Results A total of 17 927 eligible patients took part in the study (5665 had taken ondansetron before MV initiation and 12 262 patients had not). The odds ratio (OR) for 28‐day mortality for ondansetron use uncorrelated with the mediator (NLR, PLR) was 0.72 (95% confidence interval [CI] = 0.64–0.81, P < .001). Ondansetron was also associated with a reduction in 28‐day mortality after controlling for the mediator of NLR (OR = 0.98, 95% CI = 0.97–0.99, P < .01). For the indirect effect, the NLR could explain 13.47% (95% CI = 8.59–20.54%, P < .01) of the impact of ondansetron use on 28‐day mortality. The proportion mediated increased to 21.50% (95% CI = 12.36–47.44%, P < .01) for 90‐day mortality. Adjusted mediation analysis revealed no suggestion of a causal mediation pathway for this effect by the PLR (P = .12). Conclusions NLR may play substantial roles in the relationship between ondansetron pre‐treatment before initiation of mechanical ventilation and the reduction of death risk in ventilated patients.

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Tropisetron attenuates tumor growth and progression in an experimental model of mouse lung cancer

Cited by 15 publications

References 67 publications

Involvement of IL-4, IL-13 and Their Receptors in Pancreatic Cancer

Involvement of IL-4, IL-13 and Their Receptors in Pancreatic Cancer

Serotonin signalling in cancer: Emerging mechanisms and therapeutic opportunities

Mediators of neutrophil–lymphocyte ratio in the relationship between ondansetron pre‐treatment and the mortality of ICU patients on mechanical ventilation: Causal mediation analysis from the MIMIC‐IV database

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