INCONSTANT ASSOCIATION BETWEEN 27-KDA HEAT-SHOCK PROTEIN (HSP27) CONTENT AND DOXORUBICIN RESISTANCE IN HUMAN COLON-CANCER CELLS - THE DOXORUBICIN-PROTECTING EFFECT OF HSP27

To investigate the role of the small 27-kDa heat-shock protein (Hsp27) in the intrinsic resistance of colon cancer cells to doxorubicin, we modified Hsp27 expression either genetically by transfection or pharma cologically by cisplatin treatment. HT-29 cells were transfected with a full-length Hsp27 construct in the sense or antisense orientation. W e found a good correlation between cell survival after doxorubicin tre atment and Hsp27 content. A similar correlation was found for the ther moresistance of the Hsp27 transfected cells. In contrast, the sensitiv ity of the different transfected cells to 5-fluorouracil was not modif ied. cis-Platinum(II)diammine dichloride (cisplatin) treatment of HT-2 9 or Caco2 cells dramatically increased their Hsp27 mRNA and protein c ontent. Accordingly, the cells became thermoresistant. Contrary to wha t has been previously assumed, however, cell resistance to doxorubicin was reduced. Our data suggest that the decreased resistance of the ce lls to doxorubicin may be due to a concomitant increase of topoisomera se II expression, the main target of anthracyclines. In conclusion, al though Hsp27 seems to participate in the natural resistance of colon c ancer cells to anthracyclines, its increase after cisplatin treatment is not associated with a decreased cytotoxicity to doxorubicin.