Accumulation of lactosylceramide and overexpression of a PSC833-resistant P-glycoprotein in multidrug-resistant human sarcoma cells
| Autor: | Nassera Aouali, Lahcen Eddabra, Hassan El Btaouri, Claudie Madoulet, Hamid Morjani, Charles Dumontet, Sophie Malagarie-Cazenave |
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| Přispěvatelé: | Equipe 14, Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'Onco-Pharmacologie ( LOP ), Université de Reims Champagne-Ardenne ( URCA ) -JE2428, Université de Reims Champagne-Ardenne ( URCA ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Onco-Pharmacologie (LOP), Université de Reims Champagne-Ardenne (URCA)-JE2428, Université de Reims Champagne-Ardenne (URCA) |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
MESH : RNA Messenger MESH: Flow Cytometry MESH : Blotting Western MESH : Lactosylceramides MESH : P-Glycoprotein [ SDV.CAN ] Life Sciences [q-bio]/Cancer 0302 clinical medicine MESH : Tumor Cells Cultured MESH: Reverse Transcriptase Polymerase Chain Reaction Cyclosporin a Tumor Cells Cultured polycyclic compounds MESH : Cell Proliferation Cytotoxic T cell MESH: Cyclosporins MESH: Antigens CD P-glycoprotein 0303 health sciences music.instrument Antibiotics Antineoplastic biology Reverse Transcriptase Polymerase Chain Reaction MESH : Reverse Transcriptase Polymerase Chain Reaction Sarcoma General Medicine Flow Cytometry MESH: Drug Resistance Neoplasm Drug Resistance Multiple MESH : Antibiotics Antineoplastic 3. Good health MESH : Drug Resistance Neoplasm Oncology Biochemistry 030220 oncology & carcinogenesis MESH: Daunorubicin medicine.drug MESH: P-Glycoprotein Daunorubicin MESH : Flow Cytometry Blotting Western Lactosylceramides [SDV.CAN]Life Sciences [q-bio]/Cancer Cyclosporins MESH : Sarcoma MESH: Drug Resistance Multiple MESH: Doxorubicin 03 medical and health sciences Lactosylceramide Antigens CD MESH: Cell Proliferation medicine MESH : Antigens CD MESH: Blotting Western Humans MESH : Doxorubicin Doxorubicin MESH: Tumor Cells Cultured ATP Binding Cassette Transporter Subfamily B Member 1 RNA Messenger MESH : Cyclosporins MESH: Antibiotics Antineoplastic MESH: Lactosylceramides music MESH: RNA Messenger 030304 developmental biology Cell Proliferation MESH: Humans MESH : Humans Molecular biology Multiple drug resistance Cell culture Drug Resistance Neoplasm MESH: Sarcoma biology.protein MESH : Daunorubicin MESH : Drug Resistance Multiple |
| Zdroj: | Oncology Reports Oncology Reports, Spandidos Publications, 2011, 25 (4), pp.1161-7. 〈10.3892/or.2011.1180〉 Oncology Reports, Spandidos Publications, 2011, 25 (4), pp.1161-7. ⟨10.3892/or.2011.1180⟩ |
| ISSN: | 1021-335X |
| DOI: | 10.3892/or.2011.1180〉 |
| Popis: | International audience; The selection pressure for resistance to chemotherapy is accompanied by the enhanced expression of ABC proteins and increased cellular glycosphingolipid content. Thus, a possible connection between glycosphingolipid metabolism and ABC proteins in drug resistance has been suggested. In the present study, we established two human multidrug-resistant (MDR) cell lines derived from MESSA sarcoma cells by culturing with increasing concentrations of doxorubicin (DX5 cells) or doxorubicin together with cyclosporin A (GARF cells). Both resistant cell lines overexpressed the MDR1 gene and the wild-type P-glycoprotein at the same level. The cyclosporin derivative PSC833, a potent inhibitor of P-glycoprotein, sensitized DX5 but not GARF cells to the cytotoxic effects of daunorubicin. Moreover, PSC833 increased the nuclear accumulation of daunorubicin and the cellular accumulation of [3H]vinblastine in the DX5 but not in the GARF cells. The cellular incorporation of [3H]-cyclosporin A was lower in DX5 cells compared to MESSA and GARF cells, which incorporated the same level of [3H]-cyclosporin A. Sphingolipid analysis showed that the lactosylceramide level was 2.5- and 5-fold higher in DX5 and GARF cells, respectively, than in MESSA cells. Whereas the pharmacological inhibition of lactosylceramide synthesis was able to reverse only partially the resistance of GARF cells to daunorubicin without significant increase in nuclear accumulation of the drug, the same treatment before the co-treatment with PSC833 and daunorubicin increased the cytotoxic effect of daunorubicin and its nuclear accumulation. These data suggest a possible relationship between lactosylceramide levels and the resistance of P-glycoprotein to modulation by MDR modulators. |
| Databáze: | OpenAIRE |
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