Potential role of transforming growth factor beta 1 in drug resistance of tumor cells

• Autorzy: Stoika R. , Yakymovych M. , Souchelnytskyi S. , Yakymovych I.
• Języki publikacji: EN

Abstrakty

EN

Acquired drug resistance of tumor cells is frequently observed in cancer patients un­dergoing chemotherapy. We studied murine leukemia L1210 cells sensitive and resis­tant to the cytotoxic action of cisplatin and showed that cisplatin-resistant leukemia cells were also refractory to TGF /β1-dependent growth inhibition and apoptosis. Ad­dressing the question about the mechanisms responsible for the cross-resistance to cisplatin and TGF /β1, we found that cisplatin- and TGF /β1-resistant L1210 cells pos­sessed a decreased expression of type I TGF /β1 receptor, while the expression of type II TGFβ1 receptor was not affected. Western blot analysis of Smad proteins 2, 3, 4, 6, and 7, which participate in signal transduction pathway down-stream of the TGF /β1 receptors, revealed an increased expression of Smad 6, inhibiting TGF β1 action, only in cisplatin- and TGFβ1-resistant L1210 cells. TGFβ1 and especially the cytotoxic mis­tletoe agglutinin increased Smad 6 expression in TGF β1-sensitive but not in TGF /β1-resistant L1210 cells. TGF /β1-resistant L1210 cells also differed from TGF /β1-sensitive cells by the lack of expression of the pro-apoptotic p53 protein and higher level of expression of the anti-apoptotic Bcl-2 protein. Thus, the described co-expression of tumor cell refractoriness to an anti-cancer drug and to the inhibitory cytokine TGF β1 is accompanied by multiple changes in the TGF β1 signal transduction pathway and in other regulatory systems of the target cells. Besides, we found that various anti-tumor drugs and cytotoxic plant lectins increased the level of TGF β1 expression in both TGF β1-sensitive and -resistant L1210 cells. A hypothesis is proposed that TGF β1 can at least partly mediate the effect of cell-stressing agents and, thus, the development of TGF β1 resistance may be responsible for the appearance of tumor cell refractoriness to the action of some anti-cancer drugs.

Słowa kluczowe

EN

chemotherapy; drug resistance; cancer patient; tumour cell; cisplatin; transforming growth factor-beta 1

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2003
• Tom: 50
• Numer: 2
• Opis fizyczny: p.497-508,fig.

Twórcy

autor

Stoika R.

• National Academy of Sciences of Ukraine, Drahomanov Str.14-16, 79005, Lviv, Ukraine

autor

Yakymovych M.

autor

Souchelnytskyi S.

autor

Yakymovych I.

Bibliografia

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