The mediating role of AKT/ERK/JNK signaling on the malignant phenotype of microcystin-LR in gastric adenocarcinoma cells

• Published in: Food and chemical toxicology Vol. 182; p. 114174
• Main Authors: Liao, Yinghao, Deng, Yali, Yu, Xiaojin, Zhang, Peng, Liu, Ran
• Format: Journal Article
• Language: English
• Published: England 01.12.2023
• Subjects: Adenocarcinoma - chemically induced; Animals; MAP Kinase Signaling System; Microcystins - toxicity; Proto-Oncogene Proteins c-akt - metabolism; Stomach Neoplasms - chemically induced; MC-LR; Gastric adenocarcinoma cells; Toxicity pathway; Mediation effect; PI3K/AKT/ERK
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2023.114174

Microcystin-leucine arginine (MC-LR), a widely distributed and highly toxic environmental pollutant, plays crucial roles in cancer malignancy by activating characteristically toxic signaling pathways. Traditional animal-based toxicity evaluation methods have proven insufficient for identifying the specific role of these signaling pathways. Therefore, this study aimed to uncover the regulatory relationship between the toxic pathways and the progression of gastric cancer (GC). The findings provide novel avenues for conducting in vitro toxicity tests based on the investigated pathways. We found that MC-LR promoted the migration and invasion of SGC-7901 cells while simultaneously inhibiting their apoptosis in a dose-dependent manner. This observed cytotoxicity was primarily mediated through the AKT, JNK, and ERK signaling pathways. By using a mediation analysis model, we determined that AKT and ERK exhibited competitive effects in MC-LR-treated GC malignancy, while AKT and JNK acted independently from one another. This study establishes an in vitro toxicity test model of MC-LR based on toxicity-related pathways and underscores the pivotal roles of AKT, ERK, and JNK signaling in MC-LR toxicity. The findings offer a novel, fundamental framework for conducting chemical toxicity risk assessment.