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Inhibition by Erythroid Differentiation Factor (Activin A) of P-Glycoprotein Expression in Multidrug-resistant Human K562 Erythroleukemia Cells¹

Department of Chemotherapy, Saitama Cancer Center Research Institute, Ina-machi, Kitaadachi-gun, Saitama 362, [J. O-K., M. H., Y. H., M. H.], and the Institute of Applied Microbiology, the University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113 [T. T.], Japan

The K562/VCR cell line, exhibiting acquired multidrug resistance (MDR) with increased expression of a cell surface glycoprotein (P-glycoprotein), was isolated from human erythroleukemia K562 cells. Various compounds that induced erythroid differentiation of K562 cells were tested for their effects on growth and differentiation of these K562/VCR cells. Sodium butyrate, hemin, 1-ß-D-arabinofuranosylcytosine, and erythroid differentiation factor (EDF) induced erythroid differentiation of K562/VCR cells as well as K562 cells. The MDR of K562/VCR cells was partly overcome by treatment with EDF but not with the other inducers. Expression of P-glycoprotein by K562/VCR cells was measured by radioimmunoassay using MRK16 monoclonal antibody. Results showed that EDF caused down-regulation of P-glycoprotein in K562/VCR cells, whereas the other inducers did not cause its down-regulation. Thus, in addition to inducing erythroid differentiation, EDF enhanced the sensitivity of K562/VCR cells to multidrugs and suppressed expression of P-glycoprotein. These results suggest that differentiation inducers may be useful in chemotherapy of leukemic MDR cells.

¹ Supported in part by a grant for cancer research from the Ministry of Education, Science and Culture and a grant from the Ministry of Health and Welfare for a Comprehensive 10-Year Strategy for Cancer Control, Japan.

² To whom requests for reprints should be addressed.

Received 9/21/90. Accepted 3/ 5/91.

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