G6PD调控PI3K/Akt信号通路诱导肝癌细胞索拉非尼耐药的机制研究
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篇名: | G6PD调控PI3K/Akt信号通路诱导肝癌细胞索拉非尼耐药的机制研究 |
TITLE: | Study on the mechanism of G 6PD-induced sorafenib -resistance in hepatocarcinoma cell by activating PI 3K/Akt signaling pathway |
摘要: | 目的 基于磷脂酰肌醇3激酶/蛋白激酶B(PI3K/Akt)信号通路研究葡萄糖-6-磷酸脱氢酶(G6PD)诱导肝癌细胞索拉非尼耐药的机制。方法以肝癌细胞Huh7、索拉非尼耐药肝癌细胞Huh7-SR、G6PD稳定过表达的肝癌细胞Huh7-G6PD及其对照细胞Huh7-CT为研究对象,以索拉非尼或G6PD抑制剂(6-氨基烟酰胺)为干预药物,采用CCK-8法检测细胞活力,采用Westernblot法检测G6PD蛋白表达水平及PI3K/Akt信号通路相关蛋白的磷酸化水平,采用流式细胞术检测细胞凋亡水平。结果与Huh7细胞比较,Huh7-SR细胞中G6PD的表达水平显著升高(P<0.05)。经6-氨基烟酰胺和索拉非尼联合干预后,Huh7-SR细胞存活率显著降低(P<0.01)。经索拉非尼干预后,与Huh7-CT细胞比较,Huh7-G6PD细胞存活率显著升高(P<0.01),凋亡率显著降低(P<0.01)。经6-氨基烟酰胺干预后,Huh7-SR细胞中PI3K、Akt蛋白的磷酸化水平均显著降低(P<0.05)。不加药物干预时,与Huh7-CT细胞比较,Huh7-G6PD细胞中PI3K、Akt蛋白的磷酸化水平均显著升高(P<0.01)。结论G6PD可通过激活PI3K/Akt信号通路诱导肝癌细胞索拉非尼耐药。 |
ABSTRACT: | OBJECTIVE To investigate the mechanism of glucose -6-phosphate dehydrogenase (G6PD)-induced sorafenib - resistance in hepatocarcinoma cell based on phoshorylated 3-kinase/protein kinase B (PI3K/Akt)signaling pathway . METHODS Cell lines including hepatocarcinoma cell Huh 7,sorafenib-resistant cell Huh 7-SR,G6PD overexpressed cell Huh 7-G6PD and its control cell Huh 7-CT,and compounds including G 6PD inhibitor (6-Aminonicotinamide,6AN)and sorafenib were used as objects or intervention drugs in these research . CCK8 assay was applied to evaluate cell viability . The protein levels of G 6PD and the phosphorylation levels of PI 3K/Akt signaling pathway were detected by Western blot . Flow cytometry was utilized to investigate cell apoptosis. RESULTS Compared with Huh 7 cells,the protein level of G 6PD was significantly increased in Huh 7-SR cells (P< 0.05). The combination of 6AN and sorafenib reduced cell viability of Huh 7-SR cells (P<0.01). However,compared with Huh 7- CT,increased cell viability and decreased cell apoptosis rate were observed in Huh 7-G6PD cells while cells were treated with sorafenib(P<0.01). Mechanistically,the phosphorylation levels of PI 3K and Akt were significantly decreased in Huh 7-SR cells that were treated with 6AN(P<0.05). Moreover,under the condition of no drug intervention ,the phosphorylation levels of PI 3K and Akt were significantly elevated in Huh 7-G6PD cells when compared with Huh 7-CT(P<0.01). CONCLUSION G6PD could induce sorafenib -resistance in hepatocarcinoma cell by activating PI 3K/Akt signaling pathway . |
期刊: | 2022年第33卷第19期 |
作者: | 杨蕙华,陈大红,刁文婧,吴亚菲,李琴,刘皋林 |
AUTHORS: | |
关键字: | 葡萄糖-6-磷酸脱氢酶;索拉非尼;耐药;磷脂酰肌醇3激酶/蛋白激酶B信号通路;肝癌细胞 |
KEYWORDS: | glucose-6-phosphate dehydrogenase ;sorafenib;resistance;phoshorylated 3-kinase/protein kinase B signaling |
阅读数: | 216 次 |
本月下载数: | 11 次 |
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