Nitenpyram (NIT) is an insecticide used primarily for flea control in pets, especially cats and dogs. Some studies suggest that NIT is associated with cancer development, but the mechanisms involved are unclear. In this study, we integrated multi-platform bioinformatics analysis, protein-protein interaction (PPI) network construction, gene enrichment analysis and molecular docking to explore the carcinogenic mechanism of NIT in depth. We first targeted the oncogenic targets under NIT exposure, and then mapped the cross-cancer expression profiles based on 26 core genes, and quantitatively analyzed the impact weights of these genes on the prognosis of multiple malignant tumors with the help of machine learning models. Molecular docking suggested potential interactions between NIT and six proteins (KRAS, PARP1, KIT, ITGB1, EGFR, and CXCR4), with predicted binding energies below -6 kcal/mol. Single-cell transcriptomic data indicated that these genes are mainly expressed in T cells, B cells, and other immune cell subsets. Disruption of these molecules by NIT may result in reduced genetic stability, immune imbalance and disruption of cellular homeostasis, providing favorable conditions for cancer development. Finally, through integrating protein quantification analysis and cell colony formation assays, we confirmed that exposure to NIT promotes the proliferation of breast cancer cells, concomitant with an increase in PARP1 expression. Notably, short-term exposure to high doses of NIT exerts a more pronounced effect on cell proliferation.
Yin et al. (Sun,) studied this question.