Antagonism of 5-HT7 Receptors as a Promising Target for Gastric Cancer via Apoptotic Pathway

Sep 23, 2026

Although current treatment strategies improve clinical outcomes for gastric cancer, prognosis remains challenging and requires novel therapies. This study examines interactions among 5-HT7 receptors, gastric cancer, and apoptotic processes using in vitro apoptosis staining, real-time PCR, and cell proliferation assays. 5-HT7 agonist increased proliferation in primary gastric cancer cells and KATO-III cells, while the antagonist significantly inhibited proliferation and reduced NF-κB and 5-HT7 mRNA. Antagonist treatment upregulated caspase-3, caspase-9, and BAX, and enhanced apoptosis, suggesting 5-HT7 receptor–regulated apoptotic signaling as a targeted approach for combating gastric cancer.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Abstract

Introduction

Serotonin and gastric cancer background

Rationale for targeting the 5-HT7 receptor

Journal of Biochemical and Molecular Toxicology RESEARCH ARTICLE Antagonism of 5‐HT7 Receptors as a Promising Target for Gastric Cancer via Apoptotic Pathway Irfan Cinar1 | Busra Dincer2 | Elif Cadirci3 | Salih Kara4 | Mehmet Ilhan Yildirgan4 | Zekai Halici3 | Saziye Sezin Palabiyik‐Yucelik5 1Department of Pharmacology, Faculty of Medicine, Kastamonu University, Kastamonu, Türkiye | 2Department of Pharmacology, Faculty of Pharmacy, Ondokuz Mayıs University, Samsun, Türkiye | 3Department of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Türkiye | 4Department of General Surgery, Faculty of Medicine, Ataturk University, Erzurum, Türkiye | 5Department of Toxicology, Faculty of Pharmacy, Ondokuz Mayıs University, Samsun, Türkiye Correspondence: Elif Cadirci ([ecadirci@atauni.edu.tr](ecadirci@atauni.edu.tr)) Received: 24 March 2025 | Revised: 24 March 2025 | Accepted: 27 May 2025 Funding: This study was supported, in whole or in part, by the Project of The Scientific and Technological Research Council ofTürkiye (TUBITAK) (214S006) . Keywords: 5‐HT7 receptors | caspase | KATO‐III cells | LP44 | SB‐269970 ABSTRACT Although current treatment strategies have improved clinical outcomes for gastric cancer, they present a challenging prognosis that necessitates novel therapeutic approaches. The 5‐HT7 receptor, a member of the serotonin receptor family, plays a significant role in influencing the pathogenesis of various cancer types. This study seeks to investigate the complex interactions among 5‐HT7 receptors, gastric cancer, and apoptotic processes. A comprehensive set of experimental techniques was employed, including in vitro staining assays for apoptosis assessment, real‐time PCR, and cell proliferation assays. The findings indicate that the 5‐HT7 receptor agonist enhances the proliferation of primary gastric tissue cancer cells and KATO‐III cells, whereas treatment with the 5‐HT7 receptor antagonist significantly inhibits cellular proliferation. Analysis of 5‐HT7 receptor mRNA expression in gastric cancer patient populations indicated significantly elevated levels in cancerous tissues when compared to those in healthy tissues. The administration of a 5‐HT7 receptor agonist (LP44) resulted in increased cell proliferation in primary gastric cancer cells and KATO‐III cell lines, whereas treatment with a 5‐HT7 receptor antagonist (SB‐ 269970) significantly inhibited proliferation. Additionally, KATO‐III cells treated with the 5‐HT7 receptor antagonist demonstrated a marked upregulation of caspase‐3, caspase‐9, and BAX gene mRNA levels. In contrast, treatment with the 5‐HT7 receptor antagonist was associated with a significant reduction in the expression of nuclear factor kappa B and 5‐HT7 receptor mRNA levels. Annexin V‐FITC/PI and Hoechst 33342 staining demonstrated a pronounced apoptotic effect through antagonism of 5‐HT7 receptors compared to other groups. Collectively, the findings of this study suggest that the enhanced expression of 5‐HT7 receptors influences gastric cancer formation by regulating the apoptotic axis. This provides a novel perspective for understanding the molecular mechanisms underlying the potential of 5‐HT7 receptors as a targeted approach for combating gastric cancer via the apoptotic pathway. 1 | Introduction Gastric cancer (GC) stands as a formidable global health challenge, and one of the leading causes of cancer death worldwide [1] . GC is also the highest cancer burden when assessed for disability for patients and the healthcare industry. Approximately 90% of GCs are adenocarcinomas [2] . The clinical outcome for patients with advanced GC is generally poor, despite This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2025 The Author(s) . Journal of Biochemical and Molecular Toxicology published by Wiley Peri

FAQs

What is the main research goal of the study?

To evaluate whether antagonizing 5-HT7 receptors can be a promising targeted approach for gastric cancer by affecting apoptotic pathways.

How do the 5-HT7 receptor agonist and antagonist affect gastric cancer cell proliferation?

The 5-HT7 agonist increases proliferation in primary gastric cancer cells and KATO-III cells, while the 5-HT7 receptor antagonist significantly inhibits proliferation.

What apoptotic and molecular markers change after antagonist treatment?

Antagonist treatment upregulates caspase-3, caspase-9, and BAX mRNA, and reduces NF-κB and 5-HT7 receptor mRNA expression, consistent with enhanced apoptosis.

Sep 23, 2026

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