Gastric cancer is poorly-responsive to widely used antitumour drugs, the 
efficacy of which is thought to be related to the capacity of triggering 
apoptosis. This process requires a series of gene products including a 
functional p53 protein. We tested the effects of two DNA topoisomerase II 
poisons, etoposide and doxorubicin, on gastric cancer cell lines with different 
genetic lesions. We characterised MKN74 and MKN28 cells for p53 gene status and 
for the expression of p53 and p21 proteins, as well as of topoisomerase II alpha 
and beta isoforms. After drug treatments, the cells were analysed for drug 
cytotoxicity, colony forming ability, cell cycle distribution and presence of 
apoptotic features. Our findings demonstrated that both etoposide and 
doxorubicin have a potent anti-proliferative effect on gastric cancer cells. 
Cell death kinetics was different in the two cell lines, MKN74 cells being more 
sensitive than MKN28 to the drugs. MKN74 cells, although harboring a wt p53 
gene, were unable to undergo a massive apoptosis following etoposide treatment. 
The response of this cell line might be related to the topoisomerase II beta 
isozyme, the expression of which proved to be undetectable.