Chemoprevention of esophageal adenocarcinoma in a rat surgical model by a cysteinyl leukotriene receptor‑1 antagonist

Kohno,Tatsuhiko; Kinoshita,Jun; Oyama,Katsunobu; Saito,Hiroto; Shimada,Mari; Tsuji,Toshikatsu; Yamamoto,Daisuke; Moriyama,Hideki; Inaki,Noriyuki; Ohta,Tetsuo

doi:10.3892/ol.2024.14280

Chemoprevention of esophageal adenocarcinoma in a rat surgical model by a cysteinyl leukotriene receptor‑1 antagonist

Authors:
- Tatsuhiko Kohno
- Jun Kinoshita
- Katsunobu Oyama
- Hiroto Saito
- Mari Shimada
- Toshikatsu Tsuji
- Daisuke Yamamoto
- Hideki Moriyama
- Noriyuki Inaki
- Tetsuo Ohta
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Affiliations: Department of Gastrointestinal Surgery, Kanazawa University, Kanazawa, Ishikawa 920‑8641, Japan, Department of Surgery, Public Central Hospital of Matto Ishikawa, Hakusan, Ishikawa 924‑0865, Japan
Published online on: February 8, 2024 https://doi.org/10.3892/ol.2024.14280
Article Number: 147
Copyright: © Kohno et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Reflux of gastroduodenal contents into the esophagus leads to the development of esophagitis and inflammation‑associated pathologies, such as Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). The role of the lipoxygenase (LOX) pathway in carcinogenesis has been recently reported; however, its involvement in esophageal carcinogenesis remains unclear. To address this, the present study investigated the potential of pranlukast, a cysteinyl leukotriene receptor‑1 antagonist, to suppress the progression of BE and EAC in a rat duodenogastroesophageal reflux (DGER) model. Male Wistar rats that underwent DGER were divided into two groups. One group was fed commercial chow (control group), and the other was fed experimental chow containing pranlukast (pranlukast group). The rats were sacrificed at 10, 20, 30 and 40 weeks after surgery, and their esophagi were examined. Expression levels of 5‑LOX, CD68, IL‑8, VEGF and Ki‑67 were investigated using immunohistochemistry, and apoptosis was analyzed using the TUNEL method. In the pranlukast group, esophagitis was milder, and the incidence of BE and EAC was significantly lower (P<0.05) compared with that in the control group at 40 weeks after surgery. The number of cells positive for IL‑8 and VEGF were significantly lower in the pranlukast group compared with the control group. Proliferative activity was also lower in the pranlukast group compared with the control group (P<0.05). Pranlukast treatment increased apoptosis (P<0.05). Overall, Pranlukast suppressed esophageal carcinogenesis in a rat DGER model, decreasing inflammatory cytokines such as IL‑8 and VEGF.

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