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.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Stoika
R S
RS
Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv, Ukraine. stoika@cellbiol.lviv.ua
Yakymovych
I A
IA
Kashchak
N I
NI
Boyko
M M
MM
Korynevska
A V
AV
Klyuchyvska
O Yu
OY
Shafranska
G I
GI
Yakymovych
M Ya
MY
Zhylchuk
V Ye
VY
Kudryavets
Yu Y
YY
Vorontsova
A L
AL
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D008727:Methotrexate / Q000494:pharmacology; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014750:Vincristine / Q000494:pharmacology
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D053773:Transforming Growth Factor beta1; D016159:Tumor Suppressor Protein p53; D014750:Vincristine; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate