MODULATION OF ADRIAMYCIN CYTOTOXICITY ON K 562 AND K 562 ADRI BY INTERFERON-ALPHA (IFN), ALL-TRANS-RETINOIC ACID (ATRA) AND THEIR COMBINATION

Multidrug Resistant (MDR) plays a major role in chemoresistance. Alpha Interferon (IFN) and all trans retinoic acid (ATRA) have antiprolifer ative effect and IFN regulates several genes, some of them implicated in the regulation of MDR gene expression. We have studied the modulati ons of adriamycin cytotoxicity by IFN and/or ATRA; on K 562 (MDR -) an d resistant to adriamycin K 562 adri (MDR +) cell lines. We observed a n important increase of adriamycin cytotoxicity on both K 562 and K 56 2 adri by low dose of IFN and ATRA. Studies of MDR gene expression sho ws an increase in K 562 adri after exposure to IFN or ATRA. So the obs erved effect is not due to a down regulation of MDR gene expression bu t probably to the own antiproliferative effect of IFN and ATRA in comb ination with the cytotoxicity of adriamycin.