Tumour cells surviving in vivo cisplatin chemotherapy display elevated c-myc expression.
The c-myc oncogene has been extensively implicated in cell proliferation, cell differentiation and programmed cell death. Aberrant expression of the c-myc gene product has been observed in a range of tumours and has also been implicated in cisplatin (cis-dichlorodiammineplatinum)-mediated chemoresistance. A solid transplantable tumour model in syngeneic DA rats was subjected to treatment with cisplatin to determine the impact of such therapy on endogenous c-myc gene expression. Serially transplanted tumours were intravenously treated with a single cisplatin dose (1 mg/kg) and c-myc expression analysed 2 and 7 days after treatment. The surviving tumour cells display a significant 2-fold elevation in c-myc expression at 48 h and 7 days after treatment. Primary cell cultures have been derived from untreated in vivo tumours of the same model and subjected to treatment with a c-myc phosphorothioate antisense oligomer. Administration of 5 microM 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 suspension of cell growth for a period of 4 days in culture. Antisense therapies directed at the c-myc gene may well prove an effective tool for treating tumours in conjunction with cisplatin as these findings show that tumour cells surviving cisplatin chemotherapy display elevated c-myc expression.
Walker
T L
TL
Biomedical Research Group, School of Science and Technology, Charles Sturt University, Wagga Wagga NSW, Australia.
White
J D
JD
Esdale
W J
WJ
Burton
M A
MA
DeCruz
E E
EE
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D002945:Cisplatin / Q000627:therapeutic use*; D004351:Drug Resistance; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D008297:Male; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000235:genetics; D051381:Rats; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002945:Cisplatin