细胞角蛋白13通过PTEN抑制PI3K/AKT/mTOR通路增强鼻咽癌HNE1细胞放疗敏感性

目的:探讨细胞角蛋白13(cytokeratin13,CK13)对鼻咽癌HNE1细胞放疗敏感性的影响及其作用机制.方法:将HNE1细胞分为对照组、anti-CK13#a组及anti-CK13#b组(敲减CK13)、对照组+西罗莫司处理组(100nmol/L的西罗莫司处理1 h)、anti-CK13#a+西罗莫司处理组(...

Cytokeratin 13 promotes the radio-sensitivity of nasopharyngeal carcinoma HNE1 cells by inhibiting the PI3K/AKT/mTOR pathway via PTEN

Objective: To investigate the effect of cytokeratin 13(CK13) on radio-sensitivity of human nasopharyngeal carcinoma HNE1 cell line and its mechanism. Methods: HNE1 cells were divided into control group, anti-CK13#a group(CK13 knockdown),anti-CK13#b group(CK13 knockdown), control+sirolimus group(100 nmol/L sirolimus treatment for 1 h), and anti-CK13#a +sirolimus group(100 nmol/L sirolimus treatment for 1 h). After irradiation treatment(200 cGy/min irradiation for 5 min), cell proliferation in each group was measured by CCK-8 assay. Cell apoptosis rate in each group was determined by Flow cytometry.Expression of PI3K/AKT/mTOR signaling pathway related PTEN gene was detected by qPCR, and WB was used to detect the expressions of PI3K/AKT/mTOR signaling pathway related proteins. Results: In the case of radiotherapy, as compared with the control group, the proliferation of HNE1 cells after CK13 knockdown was significantly enhanced(P<0.01) while the apoptosis rate was significantly reduced(P<0.01), the contents of caspase-3 and γH2 AX as well as the protein lever of PTEN in cells were significantly decreased, while the expressions of p-AKT and p-S6 K were significantly increased(all P<0.01). Interestingly,additional treatment with sirolimus(PI3K/AKT/mTOR signaling pathway inhibitor) could rescue the accelerated cell proliferation and decreased cell apoptosis caused by CK13 knockdown(all P<0.05). Conclusion: CK13 knockdown can enhance the activity of PI3K/AKT/mTOR signaling pathway by down-regulating PTEN, and ultimately reduce the radio-sensitivity of nasopharyngeal carcinoma HNE1 cells.