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6th ESACP Congress, Heidelberg, April 7-11, 1999 |
A130
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.
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