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Sensitization of multidrug-resistant colon cancer cells to doxorubicin encapsulated in liposomes

  • Original Articles
  • Multidrug Resistance, Encapsulation, Colon Cancer Cells, Liposomes
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Summary

The effectiveness of liposome-encapsulated doxorubicin in overcoming multidrug resistance was studied in various human colon cancer cells. Colon-cancer cell lines SW403, HT29, SW620, and SW620/R overexpressed P-glycoprotein as determined by immunoflow cytometry, thereby confirming the presence of the multidrug-resistant phenotype. Important differences were observed in the cytotoxicity of free doxorubicin as represented by IC50 values of 0.168, 0.058, 0.023, and 9.83 μm for SW403, HT29, SW620, and SW620/R, respectively. Liposomally encapsulated doxorubicin provided an IC50 that was 1.4 times lower than that of the free drug in the doxorubicin-resistant SW 620/R cell line, whereas no difference was evident in the sensitive parental SW620 cells. In addition, liposomeencapsulated doxorubicin exhibited 1.31- and 2.33-fold cytotoxicity to HT-29 and SW403 cells, respectively. The ittracellular drug accumulation in SW620/R cells was enhanced by liposomally encapsulated doxorubicin, whereas it was reduced in all other cell lines as compared with that of free drug. The colon-cancer cell lines demonstrated different degrees of doxorubicin-induced DNA strand breakage that correlated with their sensitivities to drug-induced cytotoxicity. However, no difference was observed between DNA breakage caused by the free drug and that induced by liposome-encapsulated doxorubicin in any of the cell lines. The results suggest that the enhanced cytotoxicity of liposomal doxorubicin to colon cancer cells was due to some secondary non-DNA target. However, liposomally encapsulated doxorubicin appears to be effective in diminishing the multidrug-resistant phenotype and may have clinical applications.

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Authors and Affiliations

  1. Division of Clinical Pharmacology, Department of Medicine and Pharmacology, Lombardi Cancer Research Center, School of Medicine, Georgetown University, 20 007, Washington DC, USA

    Stephane Oudard & Aquilur Rahman

  2. Department of Radiation Medicine, Lombardi Cancer Research Center, School of Medicine, Georgetown University, 20 007, Washington DC, USA

    Alain Thierry & Timothy J. Jorgensen

Authors
  1. Stephane Oudard
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  2. Alain Thierry
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  3. Timothy J. Jorgensen
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  4. Aquilur Rahman
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Additional information

This work was supported in part by a grant from LyphoMed, Inc., Rosemont, Illinois (to A. R.) and by grant CA 48716 from the National Cancer Institute, National Institutes of health, DHHS (to T.J.J.)

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Oudard, S., Thierry, A., Jorgensen, T.J. et al. Sensitization of multidrug-resistant colon cancer cells to doxorubicin encapsulated in liposomes. Cancer Chemother. Pharmacol. 28, 259–265 (1991). https://doi.org/10.1007/BF00685532

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  • DOI: https://doi.org/10.1007/BF00685532

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