Objective:To investigate the molecular mechanism by which 2',4'-dihydroxychalcone(D2)inhibits proliferation,migration,and epithelial-mesenchymal transition(EMT)in colorectal cancer cells through miR-7-5p-mediated autophagy.Methods:Human colorectal cancer cell lines HCT-15 and SW620 were treated with D2 at concentrations of 0,12.5,25,and 50 μmol/L.Cell proliferation and clonogenic capacity were evaluated using MTT and colony formation assays.Cell migration was assessed by wound healing and Transwell assays.WB assay was used to detect the expression of EMT-related proteins,autophagy-related proteins,and key components of the PI3K/AKT/mTOR pathway.Autophagosome formation was visualized by immunofluorescence staining.TCGA database and KEGG pathway analyses were performed to evaluate miR-7-5p expression and its association with colorectal cancer.RT-qPCR was used to quantify miR-7-5p expression,and lentiviral transduction was employed to establish stable miR-7-5p knockdown or overexpression cell lines.Results:D2 significantly inhibited colorectal cancer cell proliferation,migration,and EMT(P<0.05 or P<0.01).TCGA and KEGG analyses revealed that miR-7-5p expression was downregulated in colorectal cancer and closely associated with disease progression.D2 treatment(12.5,25,and 50 μmol/L)significantly upregulated miR-7-5p expression in HCT-15 and SW620 cells(P<0.01).At 25 μmol/L,D2 increased the expression of autophagy-related proteins(LC3 and p-ULK1)and inhibited the PI3K/AKT/mTOR signaling pathway(P<0.05),accompanied by increased autophagosome formation(P<0.01).In miR-7-5p-knockdown cells treated with D2,the levels of LC3 and p-ULK1 were significantly reduced compared to D2-only treated cells(P<0.05 or P<0.01).Conclusion:D2 upregulates miR-7-5p to induce autophagy,thereby inhibiting colorectal cancer cell proliferation,migration,and EMT,possibly through suppression of the PI3K/AKT/mTOR signaling pathway.

Objective To establish a model of long-term atrazine(ATR)-induced liver injury in mice and to evaluate the hepatotoxic effects induced by ATR.Methods C57BL/6-N male mice were randomly divided into a control group and 1.5 mg/L and 150 mg/L ATR dose(ATR-L,ATR-H)groups.After 35 and 63 days,serum liver function biochemical indexes and inflammatory factors were detected,the hepatosomatic ratio was calculated,and the histopathology and ultrastructure of the liver were observed.Lipid peroxidation levels and antioxidant capacity,the activities of major phase I metabolic enzymes and phase Ⅱ detoxification enzymes,and the expression of related proteins in liver tissues were detected.Results Compared with the control group,the ATR groups showed significant changes in the AST/ALT ratio,levels of pro-inflammatory factors CCL2,TNF-α and IL-6,H2O2 content and activities of the metabolic enzymes NCR,CYTb5,and UDPGT(P＜0.05).In the 150 mg/L ATR group,GGT content,peroxide levels(as indicated by malondialdehyde),and CYP1A2 expression were significantly increased(P＜0.01),while GSH content was significantly decreased(P＜0.05),and hepatocyte injury and mitochondrial vacuolation were more serious when compared to control and 1.5 mg/L groups.Conclusions In a mouse model of low-dose ATR liver injury,both 1.5 mg/L and 150 mg/L ATR exposure induced liver injury in mice,with 150 mg/L ATR inducing the maximum metabolic toxicity in the liver after 63 days.