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

Stephane Oudard, Alain Thierry, Timothy J. Jorgensen, Aquilur Rahman

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)259-265
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume28
Issue number4
DOIs
StatePublished - Jul 1991
Externally publishedYes

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Liposomes
Doxorubicin
Colonic Neoplasms
Cells
Cytotoxicity
Cell Line
Pharmaceutical Preparations
Inhibitory Concentration 50
Phenotype
HT29 Cells
Multiple Drug Resistance
P-Glycoprotein
DNA

ASJC Scopus subject areas

  • Pharmacology
  • Oncology
  • Cancer Research

Cite this

Sensitization of multidrug-resistant colon cancer cells to doxorubicin encapsulated in liposomes. / Oudard, Stephane; Thierry, Alain; Jorgensen, Timothy J.; Rahman, Aquilur.

In: Cancer Chemotherapy and Pharmacology, Vol. 28, No. 4, 07.1991, p. 259-265.

Research output: Contribution to journalArticle

Oudard, Stephane ; Thierry, Alain ; Jorgensen, Timothy J. ; Rahman, Aquilur. / Sensitization of multidrug-resistant colon cancer cells to doxorubicin encapsulated in liposomes. In: Cancer Chemotherapy and Pharmacology. 1991 ; Vol. 28, No. 4. pp. 259-265.
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