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Phosphorylation of Cofilin-1 Enhances Paclitaxel Resistance of Epithelial Ovarian Cancer Cells by Inhibiting Apoptosis / 生物医学与环境科学(英文)
Biomed. environ. sci ; Biomed. environ. sci;(12): 465-477, 2021.
Article in En | WPRIM | ID: wpr-887717
Responsible library: WPRO
ABSTRACT
Objective@#To investigate the molecular mechanism of high phosphorylation levels of cofilin-1 (p-CFL-1) associated with paclitaxel resistance in epithelial ovarian cancer (EOC) cells.@*Methods@#Cells displaying varying levels of p-CFL-1 and CFL-1 were created by plasmid transfection and shRNA interference. Cell inhibition rate indicating paclitaxel efficacy was assessed by Cell Counting Kit-8 (CCK-8) assay. Apoptosis was assessed by flow cytometry and protein levels were detected by western blotting. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression levels of phosphokinases and phosphatases of CFL-1. Survival analysis evaluated the correlation between the prognosis of EOC patients and the levels of p-CFL-1 and slingshot-1 (SSH-1).@*Results@#High levels of p-CFL-1 were observed in EOC cells that survived treatment with high doses of paclitaxel. SKOV3 cell mutants with upregulated p-CFL-1 showed impaired paclitaxel efficacy, as well as decreased apoptosis rates and pro-survival patterns of apoptosis-specific protein expression. Cytoplasmic accumulation of p-CFL-1 inhibited paclitaxel-induced mitochondrial apoptosis. SSH-1 silencing mediated CFL-1 phosphorylation in paclitaxel-resistant SKOV3 cells. Clinically, the high level of p-CFL-1 and the low level of SSH-1 in EOC tissues were closely related to chemotherapy resistance and poor prognosis in EOC patients.@*Conclusion@#The SSH-1/p-CFL-1 signaling pathway mediates paclitaxel resistance by apoptosis inhibition in EOC and is expected to be a potential prognostic predictor.
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Full text: 1 Index: WPRIM Main subject: Ovarian Neoplasms / Phosphorylation / Paclitaxel / Apoptosis / Phosphoprotein Phosphatases / Drug Resistance, Neoplasm / Cell Line, Tumor / Cofilin 1 / Carcinoma, Ovarian Epithelial / Antineoplastic Agents, Phytogenic Limits: Female / Humans Language: En Journal: Biomed. environ. sci Year: 2021 Type: Article
Full text: 1 Index: WPRIM Main subject: Ovarian Neoplasms / Phosphorylation / Paclitaxel / Apoptosis / Phosphoprotein Phosphatases / Drug Resistance, Neoplasm / Cell Line, Tumor / Cofilin 1 / Carcinoma, Ovarian Epithelial / Antineoplastic Agents, Phytogenic Limits: Female / Humans Language: En Journal: Biomed. environ. sci Year: 2021 Type: Article