scholarly journals Exploration in the mechanism of fucosterol for the treatment of non-small cell lung cancer based on network pharmacology and molecular docking

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaoling Li ◽  
Baixin Lin ◽  
Zhiping Lin ◽  
Yucui Ma ◽  
Qu Wang ◽  
...  

AbstractFucosterol, a sterol isolated from brown algae, has been demonstrated to have anti-cancer properties. However, the effects and underlying molecular mechanism of fucosterol on non-small cell lung cancer remain to be elucidated. In this study, the corresponding targets of fucosterol were obtained from PharmMapper, and NSCLC related targets were gathered from the GeneCards database, and the candidate targets of fucosterol-treated NSCLC were predicted. The mechanism of fucosterol against NSCLC was identified in DAVID6.8 by enrichment analysis of GO and KEGG, and protein–protein interaction data were collected from STRING database. The hub gene GRB2 was further screened out and verified by molecular docking. Moreover, the relationship of GRB2 expression and immune infiltrates were analyzed by the TIMER database. The results of network pharmacology suggest that fucosterol acts against candidate targets, such as MAPK1, EGFR, GRB2, IGF2, MAPK8, and SRC, which regulate biological processes including negative regulation of the apoptotic process, peptidyl-tyrosine phosphorylation, positive regulation of cell proliferation. The Raf/MEK/ERK signaling pathway initiated by GRB2 showed to be significant in treating NSCLC. In conclusion, our study indicates that fucosterol may suppress NSCLC progression by targeting GRB2 activated the Raf/MEK/ERK signaling pathway, which laying a theoretical foundation for further research and providing scientific support for the development of new drugs.

2020 ◽  
Author(s):  
Xiaoling Li ◽  
Baixin Lin ◽  
Zhiping Lin ◽  
Qu Wang ◽  
Yushi Zheng ◽  
...  

Abstract Background: It has been demonstrated that fucosterol induces a therapeutic effect on cancer. However, the molecular mechanisms underlying the effects of fucosterol in the treatment of non-small cell lung cancer are still unclear.Methods: In this study, pharmMapper and GeneCards databases were utilized to gather the prediction of fucosterol targets and NSCLC-related targets. The mechanisms of fucosterol against NSCLC were identified in DAVID6.8 by enrichment analysis of GO and KEGG, and protein-protein interaction data was obtained from Sting Database. Molecular docking was used to predict the docking of GRB2. Moreover, the relationship of GRB2 expression and immune infiltrates was analyzed by TIMER database.Results: The results suggest that fucosterol acts against by candidate targets, such as MAPK1, EGFR, GRB2, IGF2, MAPK8 and SRC, which regulate biological processes including negative regulation of apoptotic process, peptidyl-tyrosine phosphorylation, positive regulation of cell proliferation. The Raf / MEK / ERK signaling pathway initiated by GRB2 maybe the most significant pathway for fucosterol to treat NSCLC.Conclusions: These results show that GRB2 is the key target for fucosterol in the treatment of NSCLC, which laying a theoretical foundation for further research and providing scientific support for the development of new drugs.


2020 ◽  
Author(s):  
Xiaoling Li ◽  
Baixin Lin ◽  
Zhiping Lin ◽  
Qu Wang ◽  
Yushi Zheng ◽  
...  

Abstract Background It has been demonstrated that fucosterol induces a therapeutic effect on cancer. However, the molecular mechanisms underlying the effects of fucosterol in the treatment of non-small cell lung cancer are still unclear.Methods In this study, pharmMapper and GeneCards databases were utilized to gather the prediction of fucosterol targets and NSCLC-related targets. The mechanisms of fucosterol against NSCLC were identified in DAVID6.8 by enrichment analysis of GO and KEGG, and protein-protein interaction data was obtained from Sting Database. Molecular docking was used to predict the docking of GRB2. Moreover, the relationship of GRB2 expression and immune infiltrates was analyzed by TIMER database.Results The results suggest that fucosterol acts against by candidate targets, such as MAPK1, EGFR, GRB2, IGF2, MAPK8 and SRC, which regulate biological processes including negative regulation of apoptotic process, peptidyl-tyrosine phosphorylation, positive regulation of cell proliferation. The Raf / MEK / ERK signaling pathway initiated by GRB2 maybe the most significant pathway for fucosterol to treat NSCLC.Conclusions These results show that GRB2 is the key target for fucosterol in the treatment of NSCLC, which laying a theoretical foundation for further research and providing scientific support for the development of new drugs.


Life Sciences ◽  
2021 ◽  
Vol 270 ◽  
pp. 119105
Author(s):  
Chong Yuan ◽  
Meng-Heng Wang ◽  
Fei Wang ◽  
Peng-Yu Chen ◽  
Xin-Ge Ke ◽  
...  

2021 ◽  
Vol 41 (3) ◽  
pp. 1231-1242
Author(s):  
SEBASTIAN GRIESING ◽  
BIN-CHI LIAO ◽  
JAMES CHIH-HSIN YANG

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jing Han ◽  
Yang Liu ◽  
Sen Yang ◽  
Xuan Wu ◽  
Hongle Li ◽  
...  

AbstractBRAF and KRAS are two key oncogenes in the RAS/RAF/MEK/MAPK signaling pathway. Concomitant mutations in both KRAS and BRAF genes have been identified in non-small cell lung cancer (NSCLC). They lead to the proliferation, differentiation, and apoptosis of tumor cells by activating the RAS/RAF/MEK/ERK signaling pathway. To date, agents that target RAS/RAF/MEK/ERK signaling pathway have been investigated in NSCLC patients harboring BRAF mutations. BRAF and MEK inhibitors have gained approval for the treatment of patients with NSCLC. According to the reported findings, the combination of MEK inhibitors with chemotherapy, immune checkpoint inhibitors, epidermal growth factor receptor-tyrosine kinase inhibitors or BRAF inhibitors is highly significant for improving clinical efficacy and causing delay in the occurrence of drug resistance. This review summarized the existing experimental results and presented ongoing clinical studies as well. However, further researches need to be conducted to indicate how we can combine other drugs with MEK inhibitors to significantly increase therapeutic effects on patients with lung cancer.


Sign in / Sign up

Export Citation Format

Share Document