Establishment of drug-resistant cell lines under the treatment with chemicals acting through different mechanisms
| Autor: | Daria S. Novikova, Viacheslav G. Tribulovich, Aleksandra Sagaidak, Aleksander Garabadzhiu, Angelina Romanova, Tatyana A. Grigoreva |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Drug Paclitaxel media_common.quotation_subject Antineoplastic Agents Drug resistance Toxicology Piperazines 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Humans ATP Binding Cassette Transporter Subfamily B Member 1 Enzyme Inhibitors P-glycoprotein media_common biology Imidazoles Biological Transport Proto-Oncogene Proteins c-mdm2 General Medicine HCT116 Cells Multiple drug resistance 030104 developmental biology Mechanism of action chemistry Cell culture Drug Resistance Neoplasm 030220 oncology & carcinogenesis biology.protein Cancer research Quinolines Efflux medicine.symptom Vanadates |
| Zdroj: | Chemico-biological interactions. 344 |
| ISSN: | 1872-7786 |
| Popis: | The problem of chemoresistance development is an inescapable flipside of modern oncotherapy, in particular for сolorectal cancer patients. The search for or development of drugs effective against resistant tumors involves the use of model resistant cell lines in vitro. To obtain such lines, we reproduced the development of chemoresistance of human colon adenocarcinoma cells under the treatment with drugs of different mechanisms, a cytostatic (paclitaxel) and a targeted agent (Nutlin-3a, an inhibitor of p53-Mdm2 protein-protein interaction). In each case, we gradually increased the content of the substance in the medium, starting from effective concentrations that do not cause total cell death. When studying the lines resistant to the corresponding drug, we noted a reduced sensitivity to the drug of another mechanism of action. Analysis of the original and resistant lines showed that the cells use the universal efflux defense mechanism. The observed effect can be partially neutralized using inhibitors of the ABC transport proteins, including P-glycoprotein, known for its oncoprotective function. The role of the latter was confirmed by real-time RT-PCR and Western blotting. |
| Databáze: | OpenAIRE |
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