Characterization of a clonal human colon adenocarcinoma line intrinsically resistant to doxorubicin
| Autor: | Agnese Molinari, M J Flens, Annarica Calcabrini, Marzia B. Gariboldi, R J Scheper, Elena Monti, T Dasdia, Giuseppe Arancia, Ersilia Dolfini |
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| Rok vydání: | 1997 |
| Předmět: |
Cancer Research
Time Factors Population Adenocarcinoma Flow cytometry medicine Tumor Cells Cultured Doxorubicin education Protein kinase C Protein Kinase C P-glycoprotein Vault Ribonucleoprotein Particles education.field_of_study biology medicine.diagnostic_test Flow Cytometry Glutathione Clone Cells Neoplasm Proteins Multiple drug resistance Oncology Biochemistry Cell culture Drug Resistance Neoplasm Colonic Neoplasms biology.protein Cancer research ATP-Binding Cassette Transporters Multidrug Resistance-Associated Proteins medicine.drug Research Article |
| Zdroj: | British Journal of Cancer |
| ISSN: | 0007-0920 |
| Popis: | Intrinsic low-level resistance to anti-cancer drugs is a major problem in the treatment of gastrointestinal malignancies. To address the problem presented by intrinsically resistant tumours, we have isolated two monoclonal lines from LoVo human colon adenocarcinoma cells: LoVo/C7, which is intrinsically resistant to doxorubicin (DOX); and LoVo/C5, which shows the same resistance index for DOX as the mixed parental cell population. For comparison, we have included in the study a LoVo-resistant line selected by continuous exposure to DOX and expressing a typical multidrug resistant (MDR) phenotype. In these cell lines we have studied the expression and/or activity of a number of proteins, including P-glycoprotein 170 (P-gp), multidrug resistance-associated protein (MRP), lung resistance-related protein (LRP), glutathione (GSH)-dependent enzymes and protein kinase C (PKC) isoforms, which have been implicated in anti-cancer drug resistance. Intracellular DOX distribution has been assessed by confocal microscopy. The results of the present study indicate that resistance in LoVo/C7 cells cannot be attributed to alterations in P-gp, LRP or GSH/GSH-dependent enzyme levels. Increased expression of MRP, accompanied by alterations in the subcellular distribution of DOX, has been observed in LoVo/C7 cells; changes in PKC isoform pattern have been detected in both intrinsically and pharmacologically resistant cells. Images Figure 2 Figure 5 Figure 6 |
| Databáze: | OpenAIRE |
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