Establishment of drug-resistant cell lines under the treatment with chemicals acting through different mechanisms.
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.
['Grigoreva|Tatyana|T|', 'Sagaidak|Aleksandra|A|', 'Romanova|Angelina|A|', 'Novikova|Daria|D|', 'Garabadzhiu|Aleksander|A|', 'Tribulovich|Viacheslav|V|']
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 D000970:Antineoplastic Agents D001692:Biological Transport D019008:Drug Resistance, Neoplasm D004791:Enzyme Inhibitors D045325:HCT116 Cells D006801:Humans D007093:Imidazoles D017239:Paclitaxel D010879:Piperazines D051736:Proto-Oncogene Proteins c-mdm2 D011804:Quinolines D014638:Vanadates
Chemoresistance Paclitaxel Nutlin-3a p53-Mdm2 P-glycoprotein Multiple drug resistance