ABSTRACT
AIM: To compare the capability of methotrexate, cisplatin, doxorubicine and vincristine to induce production of the transforming growth factor beta(1) (TGF-beta(1)) in two cell lines - MCF-7 and T47D - of human breast carcinoma, as well as to study sensitivity of these cells to TGF-beta(1) and mentioned anticancer drugs. MATERIALS AND METHODS: ELISA for detection of TGF-beta 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-beta(1) 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-beta(1) production, while doxorubicine used at a dose of 1-100 ug/ml, significantly induced TGF-beta(1) 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-beta(1). TGF-beta(1) 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-beta(1) and to cisplatine action than T47D cells, but there was no difference between these cell lines in sensitivity to other anticancer drugs.
Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/metabolism , Carcinoma/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Transforming Growth Factor beta1/metabolism , Tumor Suppressor Protein p53/metabolism , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Cisplatin/pharmacology , Doxorubicin/pharmacology , Humans , Jurkat Cells , Methotrexate/pharmacology , Mice , Transforming Growth Factor beta1/pharmacology , Vincristine/pharmacologyABSTRACT
Murine L1210 leukemia cells possessing an increased resistance to cisplatin were found to be refractory to transforming growth factor (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. These results suggest the existence of cross-resistance to cisplatin and TGF-beta1 in the studied leukemia cells.
