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

Stoika R.S., Yakymovych I.A., Kashchak N.I., Boyko M.M., Korynevska А.V., Klyuchyvska О.Yu., Shafranska G.I., Yakymovych M.Ya., Zhylchuk V.Ye., Kudryavets Yu.Y., Vorontsova A.L.

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.