Effects of decabromodiphenyl ether on genes and signaling pathways related to subcutaneous transplanted tumors of cervical cancer in mice / 预防医学

ABSTRACT

Objective@#To investigate the effects of decabromodiphenyl ether (BDE-209) on the size of subcutaneous transplanted tumors, related genes and signaling pathways of cervical cancer in mice.@*Methods@#Forty female C57BL/6 mice were subcutaneously inoculated with mouse cervical carcinoma U14 cells in the lateral axilla to establish a mouse subcutaneous transplanted tumor model. These mice were randomly divided into a high-dose group (500 mg/kg), a medium-dose group (100 mg/kg), a low-dose group (20 mg/kg) and a control group (corn oil), and were exposed to BDE-209 or corn oil by gavage. Subcutaneous transplanted tumor tissue was taken after 21 days of BDE-209 poisoning, and the differentially expressed genes in the subcutaneous transplanted tumors of cervical cancer among the four groups were analyzed by high-throughput transcriptome sequencing and were subjected to Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Protein-protein interactions (PPI) were analyzed using the STRING database, and the mRNA expression of hub genes was determined by real-time fluorescence polymerase chain reaction.@*Results@#Compared with the control group, low-dose group and medium-dose group, the mass of subcutaneous transplanted tumors in the high-dose group was decreased (all P<0.05). Transcriptome sequencing results showed that compared with the control group, 2 011 genes were up-regulated and 1 165 genes were down-regulated in the high-dose group; 960 genes were up-regulated and 357 genes were down-regulated in the medium-dose group; 537 genes were up-regulated and 262 genes were down-regulated in the low-dose group (all P<0.05). GO and KEGG analysis showed that the differentially expressed genes in the high-dose group were mainly involved in cell chemotaxis and NOD-like receptor signaling pathway; the differentially expressed genes in the medium-dose group were mainly involved in cell chemotaxis and cytokine-cytokine receptor interactions; and the differentially expressed genes in the medium-dose group were mainly involved in processing and presentation of antigens, and the signaling pathways of the complement and coagulation cascades. Compared with the control group, the mRNA expression of TLR2, MMP9, IL-6, Fos, and TNF was up-regulated in the high-dose group (all P<0.05).@*Conclusion@#High-dose BDE-209 may affect Toll-like receptors, NOD-like receptors, and other immune and inflammatory-related signaling pathways and cancer-related genes, leading to a decrease in the mass of subcutaneous transplanted cervical cancer tumors in mice.