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
;
Dahong CHEN
2
;
Wenjing DIAO
2
;
Yafei WU
2
;
Qin LI
2
;
Gaolin LIU
3
Author Information
1. School of Pharmacy，Shanghai Jiao Tong University，Shanghai 200240，China;Dept. of Clinical Pharmacy，Shanghai General Hospital，Shanghai Jiao Tong University School of Medicine，Shanghai 200080，China
2. Dept. of Clinical Pharmacy，Shanghai General Hospital，Shanghai Jiao Tong University School of Medicine，Shanghai 200080，China
3. School of Pharmacy，Shanghai Jiao Tong University，Shanghai 200240，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 .
