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- Title
下调富含脯氨酸蛋白 11 表达对食管癌耐药细胞 EC9706/DDP 耐药性的影响及其机制.
- Authors
亢春彦; 张秀芝; 周慧聪; 陈 洁
- Abstract
Objective:To discuss the effect of downregulating the proline-rich protein 11 (PRR11) expression on drug resistance of the esophageal cancer drug resistant cells, and to clarify the related mechanism. Methods:The drug resistant cells EC9706/cisplatin(DDP) were established by incrementally stimulating the human esophageal cancer EC9706 cells with the increasing concentrations of DDP. The drug sensitivity of the EC9706/DDP cells was detected by MTT assay ; the expression levels of PRR11 mRNA and protein in the EC9706/DDP cells and their parent EC9706 cells were detected by real-time fluorescence quantitative PCR (RT-qPCR) and Western blotting methods. The EC9706/DDP cells were divided into control group,sh-NC group (infected with sh-NC), sh-PRR11 group(infected with sh-PRR11), sh-NC+DDP group (infected with sh-NC and treated with 4 mg·L-1 DDP), and sh-PRR11+DDP group (infected with sh-PRR11 and treated with 4 mg·L-1 DDP) . The expression levels of PRR11 mRNA in the cells in various groups were detected by RT-qPCR method ; the expression levels of PRR11, phosphoinositide 3-kinase (PI3K) p110 α,protein kinase B (AKT), phosphorylated AKT (p-AKT), P-glycoprotein (P-gp), and multidrug resistance-associated protein 1 (MRP1) proteins in the cells in various groups were detected by Western blotting method ; the apoptotic rates of the cells in various groups were detected by flow cytometry. Results:The DDP-resistant cell line EC9706/DDP was successfully obtained,and the drug resistance index was 7. 23±0. 86. Compared with the EC9706 cells, the expression levels of PRR11 mRNA and protein in the EC9706/DDP cells were increased (P<0. 05) . Compared with control and sh-NC groups, the expression levels of PRR11 mRNA and protein in the cells in sh-PRR11 group were decreased (P<0. 05), and the 50% inhibitory concentration (IC50) of DDP was decreased (P< 0. 05) . Compared with sh-NC group, the expression levels of PI3K p110α, p-AKT, P-gp, and MRP1 proteins in the cells in sh-NC+DDP and sh-PRR11 groups were decreased (P<0. 05), and the apoptotic rate of the cells was increased (P<0. 05) . Compared with sh-NC+DDP group and sh-PRR11 group, the expression levels of PI3K p110 α, p-AKT, P-gp, and MRP1 proteins in the cells in sh-PRR11+ DDP group were increased<0. 05), and the apoptotic rate of the cells was increased<0. 05) . Conclusion : Downregulating the expression of PRR11 gene in the drug resistant EC9706/DDP cells can inhibit the expressions of drug resistance-related proteins, reverse the resistance to DDP, and induce the apoptosis ; its mechanism may be related to the inhibition of activation of the PI3K/AKT signaling pathway
- Publication
Journal of Jilin University (Medicine Edition), 2024, Vol 50, Issue 1, p113
- ISSN
1671-587X
- Publication type
Article
- DOI
10.13481/j.1671⁃587X.20240114