Overexpression of P-glycoprotein in heat- and/or drug-resistant hepatoma variants
| Autor: | Aniko Venetianer, Anna Hever-Szabo, Melinda K. Pirity |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Hot Temperature
Clinical Biochemistry Biomedical Engineering Clone (cell biology) Bioengineering Antineoplastic Agents Drug resistance Vinblastine chemistry.chemical_compound Liver Neoplasms Experimental Stress Physiological Heat shock protein Protein biosynthesis Tumor Cells Cultured Colchicine Animals HSP70 Heat-Shock Proteins ATP Binding Cassette Transporter Subfamily B Member 1 RNA Messenger RNA Neoplasm Selection Genetic P-glycoprotein Messenger RNA biology Cell Biology Molecular biology Drug Resistance Multiple Clone Cells Neoplasm Proteins Rats Multiple drug resistance chemistry Verapamil Doxorubicin Drug Resistance Neoplasm biology.protein Dactinomycin Puromycin Biotechnology |
| Zdroj: | Cytotechnology. 19(3) |
| ISSN: | 0920-9069 |
| Popis: | We have earlier isolated a glucocorticoid-resistant, dedifferentiated rat hepatoma variant, the clone 2, which exhibited deficient stress activation of the major stress-inducible heat-shock protein hsp68. Multidrug-resistant variants were isolated from clone 2 cells using increasing concentrations of colchicine. The induction deficiency of hsp68 was maintained in the colchicine-resistant clone 2 cells grown for several months in the presence of 1 microgram/ml colchicine (termed as highly multidrug-resistant variant) indicating that this heat-shock protein is not involved in the multidrug resistance. No alteration of the protein synthesis pattern was observed except the strong increase of the P-glycoprotein, which correlated with high level of corresponding mRNA. Stable heat-resistant variants of clone 2 were also isolated, which showed increased drug resistance to several drugs, i.e. they became moderately multidrug-resistant. This moderate multidrug resistance of the heat-resistant variants was further increased by stepwise selection with colchicine (highly multidrug-resistant heat-resistant variants). The levels of P-glycoprotein mRNA and protein were elevated both in the heat-resistant, non drug selected, moderately drug-resistant and in heat-resistant, colchicine selected, highly drug-resistant variants. Decreased retention of antitumor drugs was observed in all multidrug-resistant variants indicating that P-glycoprotein was functional. Verapamil increased doxorubicin retention and cytotoxicity significantly. Our results showing that severely stressed hepatoma cells overexpressed the multidrug resistance gene(s) raise the possibility that the P-glycoprotein may participate in protection against environmental stress such as heat. |
| Databáze: | OpenAIRE |
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