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

Cheppail Ramachandran, Antonieta Sauerteig, Kasi S. Sridhar, Richard J. Thurer, Awtar Krishan

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)431-441
Number of pages11
JournalCancer Chemotherapy And Pharmacology
Volume31
Issue number6
DOIs
StatePublished - Nov 1 1993

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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