安徽医科大学学报2024，Vol.59Issue(12)：2117-2126,2134,11.DOI:10.19405/j.cnki.issn1000-1492.2024.12.008
BMI1经NOTCH信号通路诱导人口腔鳞癌细胞恶性生物学行为
BMI1 induces malignant biological behavior in human oral squamous carcinoma cells via the NOTCH signaling pathway
摘要
Abstract
Objective To investigate the BMI1-NOTCH signaling pathway that regulates proliferation,migration,invasion,apoptosis,and cisplatin(CDDP)sensitivity in human oral squamous cell carcinoma(OSCC)cells.Methods Human OSCC cell line CAL27 was used to construct the CAL27 cell line with lentivirus,which knocked down or overexpressed BMI1 gene.The knockdown and control groups included:shBMI1-1,shBMI1-2,shBMI1-3,and shNC group,while the overexpression and control groups were BMI1 and NC group.RT-qPCR and Western blot were employed to verify transfection efficiency and select the cell group with the most effective knockdown.Western blot was used to detect the expression of NOTCH signaling pathway proteins,including NOTCH1,Delta-like ligand 1(DLL1),Jagged 1(JAG1),and Hairy/enhancer-of-split 1(HES1),in the transformed CAL27 cells.Subsequently,the cells in each group were cultured with the drug solvents dimethyl sulfoxide(DMSO),CDDP,NOTCH pathway inhibitor gamma-secretase inhibitor(DAPT),and CDDP+DAPT,respectively,and the cell phe-notype in each group were detected using CCK-8 assay,Wound healing assay,Transwell invasion assay,colony formation assay,and flow cytometry.Results Overexpression of BMI1 increased the expression levels of NOTCH pathway gene proteins NOTCH1,DLL1,JAG1,and HES1(P＜0.05).Under CDDP intervention,cells in the BMI1 group exhibited increased viability,invasion,migration,and colony formation abilities,and decreased apop-tosis compared to the shBMI1 group(P＜0.05).When comparing the CDDP group with the CDDP+DAPT group,the combination of medications resulted in a significant increase in the apoptosis rate and an increase in the sensitiv-ity of cancer cells to CDDP(P＜0.05).Conclusion BMI1 may increase the cellular malignancy of CAL27 cell line by activating the NOTCH signaling pathway,promoting cell viability,migration,and invasion,as well as de-creasing the cellular drug sensitivity to CDDP.Inhibition of the NOTCH pathway increases the cisplatin sensitivity of CAL27,and CDDP+DAPT has a synergistic cytotoxic effect to promote OSCC cell apoptosis.关键词
BMI1/口腔鳞状细胞癌/NOTCH/顺铂耐药/增殖/侵袭Key words
BMI1/OSCC/NOTCH/cisplatin resistance/proliferation/invasion分类
医药卫生引用本文复制引用
黄炀,马洪,向航..BMI1经NOTCH信号通路诱导人口腔鳞癌细胞恶性生物学行为[J].安徽医科大学学报,2024,59(12):2117-2126,2134,11.基金项目
贵州省卫生健康委科学技术基金项目(编号:gzwkj2023-442) Scientific and Technological Project of Guizhou Health Commission(No.gzwkj2023-442) （编号:gzwkj2023-442）
