Effect of anticancer drugs on production of transforming growth factor and expression of p53 and Bcl-2 proteins by MCF-7 and T47D cell lines of human breast carcinoma
Aim: To compare the capability of methotrexate, cisplatin, doxorubicine and vincristine to induce production of the transforming growth factor b1 (TGF- b1) in two cell lines — MCF-7 and T47D — of human breast carcinoma, as well as to study sensitivity of these cells to TGF- b1 and mentioned anticancer drugs. Materials and Methods: ELISA for detection of TGF- b content in conditioned culture media and Western-blot analysis of the proapoptotic p53 and antiapoptotic Bcl-2 proteins were applied. Results: t47d cells showing higher resistance to growth inhibiting effect of TGF- b1 were also refractory to cisplatin. There was no difference between MCF-7 and T47D cells in their sensitivity to methotrexate and doxorubicine, although T47D cells were more sensitive to vincristine. It was found that methotrexate and vincristine did not affect TGF- b1 production, while doxorubicine used at a dose of 1–100 ug/ml, significantly induced TGF- b1 production in both cell lines. p53 expression in T47D cells was higher than in MCF-7 cells where only doxorubicin induced strongly p53 expression. It should be noted, that Bcl-2 was better expressed in MCF-7 cells, while it was almost undetectable in T47D cells. Conclusion: In cells of human mammary carcinoma of MCF-7 and T47D lines doxorubicine, unlike vincristine and methotrexate, in dose depending manner induces production of TGF- b1. TGF- b1 production in carcinoma cells was associated with doxorubicine-mediated p53 expression in MCF-7 cells or high basal level of p53 in T47D cells. The cells of MCF-7 line were more sensitive to growth inhibition by exogenous TGF- b1 and to cisplatine action than T47D cells, but there was no difference between these cell lines in sensitivity to other anticancer drugs.
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