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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： | 175 次 |
| 本月下载数： | 10 次 |
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