The Impacts of Asperuloside on Epithelial-Mesenchymal Transition and Chemotherapy Resistance of Cervical Cancer Cells by Regulating the FOXO3-FOXM1 Signaling Axis
LIN Yanyun1*, LIU Haozhe2, LI Huiying1
This study was to investigate the impacts of asperuloside on EMT (epithelial-mesenchymal transition) and chemotherapy resistance of cervical cancer cells by regulating the FOXO3-FOXM1 signaling axis. Cervical cancer cells (HeLa) were separated into control (HeLa) group, drug-resistant control (HeLa/DDP) group, low concentration asperuloside group, high concentration asperuloside group, high concentration asperuloside+si-NC group, and high concentration asperuloside+si-FOXO3 group. Cell proliferation was detected using CCK-8 assay; apoptosis was detected using flow cytometry; tumor formation was observed in nude mouse transplant experiments, and FOXO3 and FOXM1 mRNA expression were detected using qRT-PCR. Western blot was used to detect the expression of epithelialmesenchymal transition related proteins N-cadherin, E-cadherin, Vimentin, and FOXO3 and FOXM1 proteins. There was no obvious difference in the proliferation and apoptosis abilities of cells between the drug-resistant control group and the control group (P>0.05). Compared with the drug-resistant control group, the expression of FOXO3 and E-cadherin, and the apoptosis rate in HeLa/DDP cells in the low concentration and high concentration asperuloside groups were increased, while the expression of FOXM1, N-cadherin, and Vimentin, and proliferation ability were decreased, the mass and volume of transplanted tumors in nude mice were reduced (P<0.05), the effect of high concentration asperuloside group was superior to the low concentration asperuloside group (P<0.05). Compared with the high concentration asperuloside+si-NC group, the expression of FOXO3 and E-cadherin, and the apoptosis rate in HeLa/DDP cells in the high concentration asperuloside+si-FOXO3 group were reduced, the expression of FOXM1, N-cadherin, Vimentin, and proliferation ability were increased, and the mass and volume of transplanted tumors in nude mice were increased (P<0.05). Asperuloside may inhibit epithelial-mesenchymal transition and chemotherapy resistance in cervical cancer HeLa cells by increasing FOXO3 expression and decreasing FOXM1 expression.
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