Effect of anticancer drugs on breast cancer cells sensitive and resistant to doxorubicin: expression of mRNAs of TGF-β and its receptors

Abstract

Comparative study of the effect of chemotherapeutic drugs (doxorubicin, methotrexate and cisplatin) and TGF-b on the human breast carcinoma MCF-7 cells, sensitive (wt) and resistant (DOX/R) to the doxorubicin action. Methods. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used for the estimation of expression of mRNAs coding for the TGF-b isoforms (TGF-b 1 and TGF-b 2) and the TGF-b type I and II receptors (TbRI and TbRII). Trypan blue exclusion method was used for measuring cell number and cell viability. Results. The MCF-7(DOX/R) cells were more refractory to the TGFb 1-dependent growth inhibition than the MCF-7(wt) cells. The level of mRNAs coding for TGF-b and its receptors was higher in the untreated MCF-7 (DOX/R) cells comparing to the MCF-7(wt) cells. The expression of mRNA coding for TbRII was decreased in both cell lines treated with doxorubicin, methotrexate and cisplatin, while the down-regulation of mRNA coding for TbRI was revealed only in the MCF-7(DOX/R) cells upon the treatment with doxorubicin and methotrexate. Conclusions. The differential effects of studied anticancer drugs and TGF-b on the doxorubicin-sensitive and-resistant cells have been demonstrated. The elucidation of the molecular mechanisms of escape of the MCF-7 (DOX/R) cells from the growth inhibition by TGF-b requires further investigation.