Study on the mechanism of G6PD-induced sorafenib-resistance in hepatocarcinoma cell by activating PI3K/Akt signaling pathway

YANG Huihua; CHEN Dahong; DIAO Wenjing; WU Yafei; LI Qin; LIU Gaolin

doi:10.6039/j.issn.1001-0408.2022.19.07

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Study on the mechanism of G6PD-induced sorafenib-resistance in hepatocarcinoma cell by activating PI3K/Akt signaling pathway

更新时间：2025-12-03

- Study on the mechanism of G6PD-induced sorafenib-resistance in hepatocarcinoma cell by activating PI3K/Akt signaling pathway
- ZHONGGUO YAOFANG Vol. 33, Issue 19, Pages: 2338-2342(2022)
- 作者机构：
  
  1.上海交通大学药学院，上海　200240
  2.上海交通大学医学院附属第一人民医院临床药学科，上海　200080
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2022.19.07
  CLC： R965;R735.7
- Received：01 April 2022，
  
  Revised：2022-08-19，
  
  Published：15 October 2022
- 稿件说明：
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杨蕙华,陈大红,刁文婧等.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 ^Δ[J].中国药房,2022,33(19):2338-2342.

YANG Huihua,CHEN Dahong,DIAO Wenjing,et al.Study on the mechanism of G6PD-induced sorafenib-resistance in hepatocarcinoma cell by activating PI3K/Akt signaling pathway[J].ZHONGGUO YAOFANG,2022,33(19):2338-2342.
杨蕙华,陈大红,刁文婧等.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 ^Δ[J].中国药房,2022,33(19):2338-2342. DOI： 10.6039/j.issn.1001-0408.2022.19.07.

YANG Huihua,CHEN Dahong,DIAO Wenjing,et al.Study on the mechanism of G6PD-induced sorafenib-resistance in hepatocarcinoma cell by activating PI3K/Akt signaling pathway[J].ZHONGGUO YAOFANG,2022,33(19):2338-2342. DOI： 10.6039/j.issn.1001-0408.2022.19.07.

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Western blot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（

＜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（

＜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（

＜0.01），凋亡率显著降低（

＜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（

＜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（

＜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 Huh7， sorafenib-resistant cell Huh7-SR， G6PD overexpressed cell Huh7-G6PD and its control cell Huh7-CT， and compounds including G6PD 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 G6PD and the phosphorylation levels of PI3K/Akt signaling pathway were detected by Western blot. Flow cytometry was utilized to investigate cell apoptosis.

RESULTS

Compared with Huh7 cells， the protein level of G6PD was significantly increased in Huh7-SR cells（

＜0.05）. The combination of 6AN and sorafenib reduced cell viability of Huh7-SR cells（

＜0.01）. However， compared with Huh7-CT， increased cell viability and decreased cell apoptosis rate were observed in Huh7-G6PD cells while cells were tre

ated with sorafenib（

＜0.01）. Mechanistically， the phosphorylation levels of PI3K and Akt were significantly decreased in Huh7-SR cells that were treated with 6AN （

＜0.05）. Moreover， under the condition of no drug intervention， the phosphorylation levels of PI3K and Akt were significantly elevated in Huh7-G6PD cells when compared with Huh7-CT（

＜0.01）.

CONCLUSION

G6PD could induce sorafenib-resistance in hepatocarcinoma cell by activating PI3K/Akt signaling pathway.

关键词

Keywords

references

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