Studying the Role and Molecular Mechanisms of MAP4K3 in Sorafenib Resistance of Hepatocellular Carcinoma
Joint Authors
Shi, Yi
Mo, Xiaofei
Hong, Simei
Li, Tianbao
Chen, Baozhen
Chen, Gang
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-11-06
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
Sorafenib is the first FDA-approved therapeutic drug for molecular target medication on advanced-stage hepatocellular carcinoma.
It is reported that sorafenib could improve the survival of progression-free patients for 4 to 6 months; however, most of the patients developed drug resistance.
Thus, it is critical to reveal the biological mechanisms behind sorafenib resistance.
In this study, a sorafenib-resistant model was developed by exposing HepG2 cells to sorafenib with gradient increasing concentration, and the resistance-related genes were screened by microarray.
Real-time qPCR was used to validate selected gene expression of the resistance model, and lentivirus vector-mediated RNA interference was applied for specific gene knockdown.
In addition, high-throughput High Celigo Select (HCS) and flow cytometry were used to measure the effect on cellular proliferation and apoptosis.
As a result, our study established a sorafenib-resistant model with IC50 of 9.988 μM.
The Affymetrix expression profile of the sorafenib-resistant model showed 35 resistant-related genes, and 91.4% of the resistant genes showed upregulation in HepG2 resistance cells.
In addition, 20 genes were knocked down to measure cell proliferation, and MAP4K3 with high proliferation inhibiting phenotype was chosen for further study.
Meanwhile, the HCS results revealed that shMAP4K3 transfection could downregulate resistant cell proliferation, and the flow cytometry results showed that cell apoptosis was significantly increased in the MAP4K3 knockdown group.
In summary, MAP4K3 is a novel molecular marker for improving the drug sensitivity of sorafenib treatment in hepatocellular carcinoma.
American Psychological Association (APA)
Shi, Yi& Mo, Xiaofei& Hong, Simei& Li, Tianbao& Chen, Baozhen& Chen, Gang. 2020. Studying the Role and Molecular Mechanisms of MAP4K3 in Sorafenib Resistance of Hepatocellular Carcinoma. BioMed Research International،Vol. 2020, no. 2020, pp.1-8.
https://search.emarefa.net/detail/BIM-1134347
Modern Language Association (MLA)
Shi, Yi…[et al.]. Studying the Role and Molecular Mechanisms of MAP4K3 in Sorafenib Resistance of Hepatocellular Carcinoma. BioMed Research International No. 2020 (2020), pp.1-8.
https://search.emarefa.net/detail/BIM-1134347
American Medical Association (AMA)
Shi, Yi& Mo, Xiaofei& Hong, Simei& Li, Tianbao& Chen, Baozhen& Chen, Gang. Studying the Role and Molecular Mechanisms of MAP4K3 in Sorafenib Resistance of Hepatocellular Carcinoma. BioMed Research International. 2020. Vol. 2020, no. 2020, pp.1-8.
https://search.emarefa.net/detail/BIM-1134347
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1134347