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<p>Diazinon (DZN) is an organophosphorus (OP) pesticide implicated in carcinogenesis. Its primary mechanism of action is inhibition of acetylcholinesterase (AChE). We evaluated the impact of low-dose DZN on two gastric cancer (GC) cell lines (AGS, MKN-45), focusing on cholinergic and serotonergic signaling. Proliferation-stimulatory concentrations were identified by MTT assay (0.1 µM for AGS, 0.01 µM for MKN-45). Scratch assays demonstrated enhanced migration at low doses but suppression at high dose. AO/EB staining confirmed reduced viability with increased apoptosis at high dose. Cell cycle analysis further revealed S-phase accumulation. qRT-PCR demonstrated upregulation of <i>CHRM3</i>,<i> SLC18A3</i>,<i> HTR2A/B</i>,<i> SLC6A4</i>,<i> BCL2</i> and <i>PCNA</i>, with concomitant downregulation of <i>ACHE</i>, <i>MAOA</i> and <i>BAX</i> in both lines; <i>HTR3A</i> and <i>HTR7</i> were selectively elevated in AGS cells. Complementary in silico analysis of gastric tumor RNA-seq data (GSE113255) confirmed differential expression of neurotransmission-related genes and enrichment of cholinergic/serotonergic pathways. Collectively, these data indicate that submicromolar DZN promotes proliferation and suppresses apoptosis of GC cells by perturbing neuronal signaling networks. Our findings provide novel evidence linking environmental OP exposure to dysregulated neurotransmitter pathways in gastric carcinogenesis and highlight neuronal signaling components as potential therapeutic or preventive targets.</p>

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Impact of pesticide diazinon on gastric cancer cell lines and the alteration of cholinergic and serotonergic pathway genes affecting cell proliferation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月18日

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  • Shadi Ghaemi,
  • Fatemeh Abedini,
  • Amir Mousavi,
  • Ghasem Ahangari

摘要

Diazinon (DZN) is an organophosphorus (OP) pesticide implicated in carcinogenesis. Its primary mechanism of action is inhibition of acetylcholinesterase (AChE). We evaluated the impact of low-dose DZN on two gastric cancer (GC) cell lines (AGS, MKN-45), focusing on cholinergic and serotonergic signaling. Proliferation-stimulatory concentrations were identified by MTT assay (0.1 µM for AGS, 0.01 µM for MKN-45). Scratch assays demonstrated enhanced migration at low doses but suppression at high dose. AO/EB staining confirmed reduced viability with increased apoptosis at high dose. Cell cycle analysis further revealed S-phase accumulation. qRT-PCR demonstrated upregulation of CHRM3, SLC18A3, HTR2A/B, SLC6A4, BCL2 and PCNA, with concomitant downregulation of ACHE, MAOA and BAX in both lines; HTR3A and HTR7 were selectively elevated in AGS cells. Complementary in silico analysis of gastric tumor RNA-seq data (GSE113255) confirmed differential expression of neurotransmission-related genes and enrichment of cholinergic/serotonergic pathways. Collectively, these data indicate that submicromolar DZN promotes proliferation and suppresses apoptosis of GC cells by perturbing neuronal signaling networks. Our findings provide novel evidence linking environmental OP exposure to dysregulated neurotransmitter pathways in gastric carcinogenesis and highlight neuronal signaling components as potential therapeutic or preventive targets.