Abstract
Objectives. To investigate the effect of anti-Fas monoclonal antibody (mAb) on the
intracellular concentration of doxorubicin in renal cell carcinoma (RCC) cells. Little
is known about the influence of anti-Fas mAb on the intracellular concentration of
chemotherapeutic agents.
Methods. The concentration of intracellular doxorubicin was determined by high-performance
liquid chromatography. The mRNA and protein levels of multidrug resistance-associated
protein gene were evaluated by reverse transcriptase-polymerase chain reaction and
immunocytochemistry, respectively.
Results. An increased concentration of doxorubicin inside the cells was found: 2.4-fold
in ACHN cells (a human RCC cell line) after treatment with doxorubicin combined with
anti-Fas mAb compared with doxorubicin alone. Of the five cases of freshly derived
RCC cells treated with doxorubicin and anti-Fas mAb, the intracellular concentration
of doxorubicin was increased 2.3 and 2.7-fold in two of them, respectively. Furthermore,
both the mRNA and the protein levels of the multidrug resistance-associated protein
gene were downregulated after treatment of ACHN cells with anti-Fas mAb. Treatment
of ACHN cells with a combination of anti-Fas mAb and doxorubicin resulted in a potentiation
of the doxorubicin-mediated cytotoxicity.
Conclusions. The increased intracellular concentration of doxorubicin by anti-Fas
mAb might be one of the mechanisms responsible for the enhancement of doxorubicin-mediated
cytotoxicity in RCC cells.
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Article info
Publication history
Accepted:
January 12,
2001
Received in revised form:
January 12,
2001
Received:
October 16,
2000
Identification
Copyright
© 2001 Elsevier Science Inc. Published by Elsevier Inc. All rights reserved.
