6th ESACP Congress, Heidelberg, April 7-11, 1999

A130
CROSS RESISTANCE TO CISPLATIN AND TRANSFORMING GROWTH FACTOR BETA 1 IN MURINE L1210 LEUKEMIA CELLS
Stoika RS, Yakymovych MY, Yakymovych IA

Division of Regulatory Cell Systems, Institute of Biochemistry, National Academy of Sciences of Ukraine, Lviv, Ukraine

The development of resistance to chemotherapeutic treatment of neoplastic diseases limits the efficacy of drugs. Cisplatin is an effective antineoplastic medicine used for the treatment of a variety of tumors. Although different biochemical mechanisms have been proposed for the explanation of cisplatin resistance, up to now any of these mechanism has been accepted as a universal. A positive correlation was found between the malignant potential of the tumor cells and their resistance to transforming growth factor-beta (TGF-beta) 1 growth inhibition. Here we show that murine L1210 leukemia cells possessing an increased resistance to cisplatin action are also refractory to TGF-beta1-induced growth inhibition, while the parental L1210 cells were strongly inhibited by this cytokine. Growth inhibition was estimated on the basis of [3H]-thymidine incorporation, cell counting, and colony-forming assay. Cisplatin-resistant L1210 cells were also shown to be much more resistant than the parental cells to both cisplatin- and TGF-beta1-induced apoptosis detected by DNA electrophoresis in the agarose gel. Thus, we found a positive correlation between the resistance of murine leukemia L1210 cells to the antitumor drug cisplatin action and their resistance to the growth inhibitory and apoptosis-inducing effects of TGF-beta1 which suggests a novel mechanism of cisplatin action in these tumor cells.