Relationship between proliferation and invasion of human colorectal cancer induced by dichlorodiphenyltrichloroethane and expression of miR-129/CDK-14

Abstract

Abstract: Objective To investigate the relationship between the proliferation and invasion of human colorectal cancer induced by dichlorodiphenyltrichloroethane（DDT） and the expression of microRNA-129（miR-129）/cyclin-dependent kinase-14（CDK-14）. Methods The human colorectal cancer cells with a density of 5×10⁶/mL were treated with DDT at final concentrations of 0.0,100,250,and 500 nmol/L for 72 hours,respectively. The cell viability and cell colony were determined by the 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphenyl-2-H-tetrazolium bromide（MTT） method and methyl violet staining. The apoptosis level was measured by flow cytometry. The invasion and migration levels of cells were measured by transwell chamber（Transwell） and scratch assay. The levels of miR-129,CDK-14,coiled-coil domain-34（CCDC34） and Galactokinase 1（GALK1） were measured by real-time fluorescent reverse transcription（RT-PCR） and Western blotting method. Results The cell proliferation level[（70.59±7.72,76.63±8.32,84.25±9.04 vs 62.58±6.83）%],cell colony（99.95±9.58,215.63±19.85,398.96±35.26 vs 62.63±6.52）,invasion number（76.25±9.58, 154.62±19.51,298.96±38.57 vs 49.65±6.65）,migration level（75.96±14.58,119.69±20.59,165.63±32.68 vs 11.59±2.28）,as well as CDK-14,CCDC34,GALK1 mRNA protein levels in 100,250,500 nmol/L DDT groups were significantly higher than those in the control group（P<0.01）,and the apoptosis rate and miR-129 level were significantly lower than those in the control group（P<0.01）. The cell proliferation level,cell colony,invasion number,migration level,CDK-14 mRNA protein[（1.60±0.28,2.14±0.33,2.99±0.51 vs 0.92±0.16）,（0.42±0.07,0.85±0.14,1.20±0.20 vs 0.21±0.03）],CCDC34（0.48±0.08,0.87±0.15,1.18±0.18 vs 0.28±0.07）,GALK1（0.50±0.09,0.84±0.14,1.22±0.19 vs 0.30±0.08） protein levels in 500 nmol/LDDT group were higher than those in 250 nmol/L DDT group,and the differences were statistically significant（all P<0.01）. The apoptosis rate（1.70±0.31,1.00±0.16, 0.60±0.11 vs 3.00±0.51） and miR-129（1.42±0.24,0.92±0.15,0.64±0.10 vs 1.78±0.28） level were lower than those in 250 nmol/L DDT group,and the differences were statistically significant（all P<0.01）.The cell proliferation level,cell colony,invasion number, migration level,CDK-14,CCDC34,and GALK1 mRNA protein levels in 250 nmol/L DDT group were higher than those in 100 nmol/L DDT group,and the differences were statistically significant（all P<0.01）. The apoptosis rateand miR-129 level in 250 nmol/L DDT group were lower than those in 100 nmol/L DDT group,and the differences were statistically significant（all P<0.01）. There was a significant dose-response relationship between DDT concentration and cell proliferation level,cell colony,invasion number,migration level,apoptosis rate,miR-129 level,CDK-14,CCDC34,GALK1 mRNA protein level（P<0.01）. Conclusion DDT down-regulates the expression of miR-129 and targets to up-regulate the expression of CDK-14,CCDC34 and GALK1,thereby promoting the proliferation and invasion of colorectal cancer cells and inhibiting their apoptosis.

Key words: Dichlorodiphenyltrichloroethane, Colorectum, MicroRNA-129, Cyclin-dependent kinase-14

CLC Number:

R114

PU Zhizhong, WU Wan. Relationship between proliferation and invasion of human colorectal cancer induced by dichlorodiphenyltrichloroethane and expression of miR-129/CDK-14. [J]OCCUPATION AND HEALTH, 2023, 39(19): 2626-2632.

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