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

Exp Oncol. 2008 Mar;30(1):35-41.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / metabolism*
  • Carcinoma / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cisplatin / pharmacology
  • Doxorubicin / pharmacology
  • Humans
  • Jurkat Cells
  • Methotrexate / pharmacology
  • Mice
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Transforming Growth Factor beta1 / metabolism*
  • Transforming Growth Factor beta1 / pharmacology
  • Tumor Suppressor Protein p53 / metabolism*
  • Vincristine / pharmacology


  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Transforming Growth Factor beta1
  • Tumor Suppressor Protein p53
  • Vincristine
  • Doxorubicin
  • Cisplatin
  • Methotrexate