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

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

  • J Cell Biochem. 2020 Feb;121(2):1610-1622. doi: 10.1002/jcb.29395.
Mohsen Rashidi 1 2 Ali Bazi 3 Mohammad R Shiran 1 Abouzar Bagheri 2 4 Abbas R Mehrabadi 5 Hadi Kalantar 6 Zahra Ghafouri 4 Sayed M Hosseini 7
Affiliations

Affiliations

  • 1 Department of Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
  • 2 Molecular and Cell Biology Research Center, Faculty Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
  • 3 Department of Hematology, Faculty of Allied Medical Sciences, Zabol University of Medical Sciences, Zabol, Iran.
  • 4 Department of Clinical Biochemistry-Biophysics and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
  • 5 Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada.
  • 6 Department of Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
  • 7 Human Genetic Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Abstract

The antineoplastic effects of 5-hydroxytryptamine (5-HT) receptor antagonists have been shown in previous studies. However, the exact underlying mechanisms mediating these antineoplastic effects are unclear. In the present study, we assessed the antineoplastic effects of tropisetron, a 5-HT Receptor Antagonist, in an experimental model of lung Cancer in BALB/c mouse. Lewis lung carcinoma cell line was used to induce lung Cancer. Mice were divided into four groups (n = 6) as follows: tumor-bearing mice + tropisetron (5 mg/kg intraperitoneally [IP]), tumor-bearing mice + tropisetron (10 mg/kg IP), tumor-bearing mice + saline, healthy mice + tropisetron (10 mg/kg). Tumor burden, interferon-γ (IFN-γ), interleukin (IL)-4, pathological response, Ki-67, and E-cadherin were assessed using enzyme-linked immunosorbent assay, and real-time polymerase chain reaction. Comet assay was used to assess DNA toxicity. Tropisetrone-treated Animals (either 5 or 10 mg/kg) showed significantly lower tumor sizes at the day 24th after tumor induction. Tropisetron received Animals also showed significantly higher levels of IFN-γ, E-cadherin, pathologic response, and necrotic cells compared to the saline-treated counterparts. In addition, the levels of IL-4, and Ki-67 were significantly lower in tropisetrone treated mice in comparison with control. Furthermore, tropisteron coadministration signifcantly reduced H2 O2 -induced DNA toxicity while treatment with tropisteron alone showed no adverse effect on DNA. Tropisetrone can be used as a potential antineoplastic drug in lung Cancer. This agent can promote its antineoplastic effects in part through modulating inflammatory and proliferating markers.

Keywords

lung cancer; mice; neoplasms; tropisetron.

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