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Tropisetron attenuates tumor growth and progression in an experimental model of mouse lung cancer
Author(s) -
Rashidi Mohsen,
Bazi Ali,
Shiran Mohammad R.,
Bagheri Abouzar,
Mehrabadi Abbas R.,
Kalantar Hadi,
Ghafouri Zahra,
Hosseini Sayed M.
Publication year - 2020
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.29395
Subject(s) - tropisetron , pharmacology , lewis lung carcinoma , lung cancer , medicine , cancer , cancer research , biology , pathology , receptor , antagonist , metastasis
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 H 2 O 2 ‐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.