TUMOR-CELLS SURVIVING IN-VIVO CISPLATIN CHEMOTHERAPY DISPLAY ELEVATEDC-MYC EXPRESSION

The c-myc oncogene has been extensively implicated in cell proliferati on, cell differentiation and programmed cell death. Aberrant expressio n of the c-myc gene product has been observed in a range of rumours an d has also been implicated in cisplatin (cis-dichlorodiammineplatinum) -mediated chemoresistance. A solid transplantable tumour model in syng eneic DA rats was subjected to treatment with cisplatin to determine t he impact of such therapy on endogenous c-myc gene expression. Seriall y transplanted tumours were intravenously treated with a single cispla tin dose (1 mg kg(-1)) and c-myc expression analysed 2 and 7 days afte r treatment. The surviving tumour cells display a significant 2-fold e levation in c-myc expression at 48 h and 7 days after treatment. Prima ry cell cultures have been derived from untreated in vivo rumours of t he same model and subjected to treatment with a c-myc phosphorothioate antisense oligomer. Administration of 5 mu M c-myc antisense oligomer directed at the initiation codon and first four codons of c-myc mRNA results in total inhibition of c-myc expression and coincident suspens ion of cell growth for a period of 4 days in culture. Antisense therap ies directed al the c-myc gene may well prove an effective tool for tr eating tumours in conjunction with cisplatin as these findings show th at tumour cells surviving cisplatin chemotherapy display elevated c-my c expression.