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MDR-1 gene expression, anthracycline retention and cytotoxicity in human lung-tumor cells from refractory patients

  • Original Articles
  • Anthracycline, Cytotoxicity, MDR-1 Gene Expression, Human Lung-tumor Cells
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Summary

Lung-tumor cells from pleural effusion of four refractory patients and in cell lines established from them were analyzed for anthracycline retention, cytotoxicity, and MDR-1 gene and P-glycoprotein expression. Murine leukemic P388 and doxorubicin-resistant P388/R84 lines were used as controls. The 50% growth-inhibitory concentration (IC50) for doxorubicin among lung-tumor lines varied from 0.16 to 0.31 μM in soft agar. Heterogeneity in doxorubicin or daunorubicin retention and response to the efflux-blocking action of 25 μm prochlorperazine was noted in pleural effusion of FCCL-1,-4, and-8. Among the cell lines established, an efflux-blocking effect in a subpopulation was noticed only in FCCL-1 and-4. Although the MDR-1 gene was present in all cell lines, including P388, its expression was pronounced only in P388/R84 and FCCL-1. In situ hybridization of antisense RNA probe to tumor cells showed high heterogeneity for MDR-1 message in the human lung-tumor cells as compared with the murine cells. Northern and slot blot hybridization confirmed in situ hybridization in lines with high levels of MDR-1 expression. The synthesis of MDR-1 mRNA and P-glycoprotein in tumor lines was correlated. The results suggest that because of extensive tumor-cell heterogeneity in human tumors, monitoring of MDR expression by in situ hybridization, quantitation of P0glycoprotein content by laser flow cytometry (and/or immunohistochemical methods), and drug efflux (by laser flow cytometry) may be the best ways to monitor multidrug resistance in human tumors.

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Authors and Affiliations

  1. Department of Radiation Oncology, University of Miami Medical School, P. O. Box 016960 (R-71), 33101, Miami, Florida, USA

    Cheppail Ramachandran, Antonieta Sauerteig & Awtar Krishan

  2. Department of Medicine, University of Miami Medical School, Miami, Florida, USA

    Kasi S. Sridhar

  3. Department of Surgery, University of Miami Medical School, Miami, Florida, USA

    Richard J. Thurer

Authors
  1. Cheppail Ramachandran
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  2. Antonieta Sauerteig
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  3. Kasi S. Sridhar
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  4. Richard J. Thurer
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  5. Awtar Krishan
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This work was supported by NIH grant CA-R01 44737

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Ramachandran, C., Sauerteig, A., Sridhar, K.S. et al. MDR-1 gene expression, anthracycline retention and cytotoxicity in human lung-tumor cells from refractory patients. Cancer Chemother. Pharmacol. 31, 431–441 (1993). https://doi.org/10.1007/BF00685031

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  • DOI: https://doi.org/10.1007/BF00685031

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