Rapid screening of multi-target antitumor drugs by nonimmobilized tumor cells/tissues capillary electrophoresis
Copyright © 2018 Elsevier B.V. All rights reserved..
As there are more target categories on tumor cells/tissues than on receptor-overexpressing cells, and tumor tissues can better simulate TME, we established a new method of screening multi-target antitumor drugs by nonimmobilized tumor cells/tissues capillary electrophoresis under approximately tumor physiological environment. In this method, the natural structure and active conformation of the target proteins on tumor cells/tissues can be well maintained without separation and purification. Therefore, we successfully used this method to study the interactions between the Aidi injection (ADI)/its main components and tumor cells/tissues by optimizing a series of experimental conditions, discovered seven components with binding activity to A549 cells, five of them with specific interaction to tumor tissues, and calculated the binding kinetic parameters (K, ka, kd, and k'). Then, antitumor activity assays in vitro and in vivo were carried out to discover a new drug combination with higher targeting, better pharmaceutical efficacy, and lower toxic side effects. Finally, molecular docking studies were performed to investigate the potential target groups of the interactions between the effective drug combination and A549 cells/tissues. In summary, the method was verified to be valid and feasible, and can be easily transferred to a capillary array electrophoresis for high-throughput drug screening.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:1045 |
|---|---|
| Enthalten in: |
Analytica chimica acta - 1045(2019) vom: 03. Jan., Seite 152-161 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Wu, Ruijun [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Antineoplastic Agents |
|---|
| Anmerkungen: |
Date Completed 03.04.2019 Date Revised 03.04.2019 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.aca.2018.09.015 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM290862892 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM290862892 | ||
| 003 | DE-627 | ||
| 005 | 20231225065633.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.aca.2018.09.015 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0969.xml |
| 035 | |a (DE-627)NLM290862892 | ||
| 035 | |a (NLM)30454570 | ||
| 035 | |a (PII)S0003-2670(18)31084-5 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Wu, Ruijun |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Rapid screening of multi-target antitumor drugs by nonimmobilized tumor cells/tissues capillary electrophoresis |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 03.04.2019 | ||
| 500 | |a Date Revised 03.04.2019 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2018 Elsevier B.V. All rights reserved. | ||
| 520 | |a As there are more target categories on tumor cells/tissues than on receptor-overexpressing cells, and tumor tissues can better simulate TME, we established a new method of screening multi-target antitumor drugs by nonimmobilized tumor cells/tissues capillary electrophoresis under approximately tumor physiological environment. In this method, the natural structure and active conformation of the target proteins on tumor cells/tissues can be well maintained without separation and purification. Therefore, we successfully used this method to study the interactions between the Aidi injection (ADI)/its main components and tumor cells/tissues by optimizing a series of experimental conditions, discovered seven components with binding activity to A549 cells, five of them with specific interaction to tumor tissues, and calculated the binding kinetic parameters (K, ka, kd, and k'). Then, antitumor activity assays in vitro and in vivo were carried out to discover a new drug combination with higher targeting, better pharmaceutical efficacy, and lower toxic side effects. Finally, molecular docking studies were performed to investigate the potential target groups of the interactions between the effective drug combination and A549 cells/tissues. In summary, the method was verified to be valid and feasible, and can be easily transferred to a capillary array electrophoresis for high-throughput drug screening | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Drug screening | |
| 650 | 4 | |a Multi-target drug combinations | |
| 650 | 4 | |a Nonimmobilized tumor cells/tissues capillary electrophoresis | |
| 650 | 4 | |a Target groups | |
| 650 | 4 | |a Tumor microenvironment | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 700 | 1 | |a Li, Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Cong |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Jinyu |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Xiaozhi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Sufang |e verfasserin |4 aut | |
| 700 | 1 | |a Zou, Juncheng |e verfasserin |4 aut | |
| 700 | 1 | |a Ling, Xiaomei |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Analytica chimica acta |d 1966 |g 1045(2019) vom: 03. Jan., Seite 152-161 |w (DE-627)NLM000012637 |x 1873-4324 |7 nnns |
| 773 | 1 | 8 | |g volume:1045 |g year:2019 |g day:03 |g month:01 |g pages:152-161 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.aca.2018.09.015 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 1045 |j 2019 |b 03 |c 01 |h 152-161 | ||