Study on the mechanism of G 6PD-induced sorafenib -resistance in hepatocarcinoma cell by activating PI 3K/Akt signaling pathway
- VernacularTitle: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
- Author:
Huihua YANG
1
,
2
;
Dahong CHEN
2
;
Wenjing DIAO
2
;
Yafei WU
2
;
Qin LI
2
;
Gaolin LIU
1
Author Information
1. School of Pharmacy，Shanghai Jiao Tong University，Shanghai 200240，China
2. Dept. of Clinical Pharmacy，Shanghai General Hospital，Shanghai Jiao Tong University School of Medicine，Shanghai 200080，China
- Publication Type:Journal Article
- Keywords:
glucose-6-phosphate dehydrogenase;
sorafenib;
resistance;
phoshorylated 3-kinase/protein kinase B signaling
- From:
China Pharmacy
2022;33(19):2338-2342
- CountryChina
- Language:Chinese
-
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 .
