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Anti-Tumor Potential of a 5-HT3 Receptor Antagonist as a Novel Autophagy Inducer in Lung Cancer: A Retrospective Clinical Study with In Vitro Confirmation

 Jeong Soo Lee  ;  Seong Yong Park  ;  Na Young Kim  ;  Dong Wook Kim  ;  Ju Eun Oh  ;  Eunjin Heo  ;  Jong Seok Lee  ;  Young Chul Yoo 
 Journal of Clinical Medicine, Vol.8(9) : E1380, 2019 
Journal Title
Issue Date
lung neoplasm ; palonosetron ; ramosetron ; serotonin antagonist
Unlike 5-hydroxytryptamine (5-HT, serotonin) 1 and 5-HT2, the effect of 5-HT3 receptors on tumor cells is poorly understood. We conducted this study to determine whether the perioperative use of 5-HT3 receptor antagonists, which are widely used antiemetics, impacts the recurrence and mortality after lung cancer surgery and related anti-tumor mechanisms. From data on 411 patients, propensity score matching was used to produce 60 1:2 matched pairs of patients, and variables associated with the prognosis after open lung cancer surgery were analyzed. Additionally, the effects of 5-HT3 receptor antagonists were confirmed in vitro on A549 human lung adenocarcinoma cells. Cancer recurrence occurred in 10 (8.2%) and 14 (22.95%) patients (p = 0.005), treated or untreated, with palonosetron or ramosetron. Perioperative usage of palonosetron or ramosetron was also associated with lower recurrence rate after lung cancer surgery (hazard ratio (HR), 0.293; 95% confidence interval (CI) 0.110-0.780, p = 0.0141). Our in vitro experiments also showed that palonosetron and ramosetron inhibited cell proliferation and colony formation and reduced migration, which was associated with autophagic cell death via the extracellular signal-regulated kinase (ERK) pathway. Palonosetron and ramosetron may have anti-tumor potential against lung cancer cells, suggesting the need to consider these drugs as first-choice antiemetics in patients undergoing lung cancer surgery.
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1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Na Young(김나영) ORCID logo https://orcid.org/0000-0003-3685-2005
Park, Seong Yong(박성용) ORCID logo https://orcid.org/0000-0002-5180-3853
Oh, Ju Eun(오주은)
Yoo, Young Chul(유영철) ORCID logo https://orcid.org/0000-0002-6334-7541
Lee, Jeong Soo(이정수) ORCID logo https://orcid.org/0000-0002-8947-3706
Lee, Jong Seok(이종석) ORCID logo https://orcid.org/0000-0002-7945-2530
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