Effects of topoisomerase II inhibitors on gastric cancer cells characterized by different genetic lesions

Gastric cancer is poorly-responsive to widely used antitumour drugs, the ef ficacy of which is thought to be related to the capacity of triggering apop tosis. This process requires a series of gene products including a function al p53 protein. We tested the effects of two DNA topoisomerase II poisons, etoposide and doxorubicin, on gastric cancer cell lines with different gene tic 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 fo r drug cytotoxicity, colony forming ability, cell cycle distribution and pr esence 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 harbor ing a wt p53 gene, were unable to undergo a massive apoptosis following eto poside treatment. The response of this cell line might be related to the to poisomerase II beta isozyme, the expression of which proved to be undetecta ble.