Effect of Electric Fields on the Mechanical Mechanism of Regorafenib–VEGFR2 Interaction to Enhance Inhibition of Hepatocellular Carcinoma
The interaction between molecular targeted therapy drugs and target proteins is crucial with regard to the drugs’ anti-tumor effects. Electric fields can change the structure of proteins, which determines the interaction between drugs and proteins. However, the regulation of the interaction between...
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MDPI AG
2025-01-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/15/1/42 |
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| author | Yichen Tian Fenghui Liao Heng Sun Yongrong Lei Yuna Fu Feng Xia Jianhua Wang |
| author_facet | Yichen Tian Fenghui Liao Heng Sun Yongrong Lei Yuna Fu Feng Xia Jianhua Wang |
| author_sort | Yichen Tian |
| collection | DOAJ |
| description | The interaction between molecular targeted therapy drugs and target proteins is crucial with regard to the drugs’ anti-tumor effects. Electric fields can change the structure of proteins, which determines the interaction between drugs and proteins. However, the regulation of the interaction between drugs and target proteins and the anti-tumor effects of electric fields have not been studied thoroughly. Here, we explored how electric fields enhance the inhibition of regorafenib with regard to the activity, invasion, and metastasis of hepatocellular carcinoma cells. We found that electric fields lead to an increase in the normal (adhesion) and transverse (friction) interaction forces between regorafenib and VEGFR2. In single molecule pair interactions, there are changes in specific and nonspecific forces. Hydrogen bonds, hydrophobic interactions, and van der Waals forces are the main influencing factors. Importantly, the increase in the adhesion force and friction force between regorafenib and VEGFR2 caused by electric fields is related to the activity and migration ability of hepatocellular carcinoma cells. The morphological changes in VEGFR2 prove that electric fields regulate protein conformation. Overall, our work proves the drug–protein mechanical mechanism by which electric fields enhance the anti-tumor effect of regorafenib and provides insights into the application of electric fields in clinical tumor treatment. |
| format | Article |
| id | doaj-art-8b2d8f65e45647c88243c812d8687676 |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-8b2d8f65e45647c88243c812d86876762025-01-24T13:24:57ZengMDPI AGBiomolecules2218-273X2025-01-011514210.3390/biom15010042Effect of Electric Fields on the Mechanical Mechanism of Regorafenib–VEGFR2 Interaction to Enhance Inhibition of Hepatocellular CarcinomaYichen Tian0Fenghui Liao1Heng Sun2Yongrong Lei3Yuna Fu4Feng Xia5Jianhua Wang6Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, ChinaKey Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, ChinaKey Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, ChinaKey Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, ChinaKey Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, ChinaKey Laboratory of Hepatobiliary and Pancreatic Surgery, Institute of Hepatobiliary Surgery, Southwest Hospital, The First Hospital Affiliated to AMU (Southwest Hospital), Chongqing 400038, ChinaKey Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, ChinaThe interaction between molecular targeted therapy drugs and target proteins is crucial with regard to the drugs’ anti-tumor effects. Electric fields can change the structure of proteins, which determines the interaction between drugs and proteins. However, the regulation of the interaction between drugs and target proteins and the anti-tumor effects of electric fields have not been studied thoroughly. Here, we explored how electric fields enhance the inhibition of regorafenib with regard to the activity, invasion, and metastasis of hepatocellular carcinoma cells. We found that electric fields lead to an increase in the normal (adhesion) and transverse (friction) interaction forces between regorafenib and VEGFR2. In single molecule pair interactions, there are changes in specific and nonspecific forces. Hydrogen bonds, hydrophobic interactions, and van der Waals forces are the main influencing factors. Importantly, the increase in the adhesion force and friction force between regorafenib and VEGFR2 caused by electric fields is related to the activity and migration ability of hepatocellular carcinoma cells. The morphological changes in VEGFR2 prove that electric fields regulate protein conformation. Overall, our work proves the drug–protein mechanical mechanism by which electric fields enhance the anti-tumor effect of regorafenib and provides insights into the application of electric fields in clinical tumor treatment.https://www.mdpi.com/2218-273X/15/1/42mechanical mechanismregorafenibVEGFR2electric fieldshepatocellular carcinomaAFM |
| spellingShingle | Yichen Tian Fenghui Liao Heng Sun Yongrong Lei Yuna Fu Feng Xia Jianhua Wang Effect of Electric Fields on the Mechanical Mechanism of Regorafenib–VEGFR2 Interaction to Enhance Inhibition of Hepatocellular Carcinoma Biomolecules mechanical mechanism regorafenib VEGFR2 electric fields hepatocellular carcinoma AFM |
| title | Effect of Electric Fields on the Mechanical Mechanism of Regorafenib–VEGFR2 Interaction to Enhance Inhibition of Hepatocellular Carcinoma |
| title_full | Effect of Electric Fields on the Mechanical Mechanism of Regorafenib–VEGFR2 Interaction to Enhance Inhibition of Hepatocellular Carcinoma |
| title_fullStr | Effect of Electric Fields on the Mechanical Mechanism of Regorafenib–VEGFR2 Interaction to Enhance Inhibition of Hepatocellular Carcinoma |
| title_full_unstemmed | Effect of Electric Fields on the Mechanical Mechanism of Regorafenib–VEGFR2 Interaction to Enhance Inhibition of Hepatocellular Carcinoma |
| title_short | Effect of Electric Fields on the Mechanical Mechanism of Regorafenib–VEGFR2 Interaction to Enhance Inhibition of Hepatocellular Carcinoma |
| title_sort | effect of electric fields on the mechanical mechanism of regorafenib vegfr2 interaction to enhance inhibition of hepatocellular carcinoma |
| topic | mechanical mechanism regorafenib VEGFR2 electric fields hepatocellular carcinoma AFM |
| url | https://www.mdpi.com/2218-273X/15/1/42 |
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