N Yu Lukyanova1. 1. R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine. oncom@onconet.kiev.ua
Abstract
AIM: To study the influence of homocysteine on the mechanisms of drug resistance formation. METHODS: In current study human MCF-7 breast cancer cells and A2780 ovarian cancer cells sensitive to anticancer drugs were used. To access the viability of cells, we applied 3-[4,5-dimethylthiazol-2-1]-2,5-diphenyltetrazolium bromide colorimetric assay (MTT-test). Expression of Bcl-2, p-glycoprotein (P-gp), glutathione S-transferase (GST) and E-cadherin was studied by immunocytochemistry. RESULTS: A2780 and MCF-7 cells were treated by homocysteine. It was shown that every next treatment with homocysteine (up to 5th) decreased the sensitivity of A2780 and MCF-7 cells to cytotoxic drugs. Immunocytochemical study of molecular profile of A2780 and MCF-7 cells after long-term cultivation with homocysteine has been carried out and has revealed that such treatment resulted in the induction of Bcl-2, P-gp, GST and E-cadherin expression. This indicates that incubation of studied cells with homocysteine leads to simultaneous induction of expression of drug resistance markers to cisplatin and doxorubicin. CONCLUSION: Cultivation of MCF-7 and A2780 cells with homocysteine leads to simultaneous development of resistance to doxorubicine and cisplatin. The development of drug resistance is diverse for different drugs and varies among cell lines.
AIM: To study the influence of homocysteine on the mechanisms of drug resistance formation. METHODS: In current study humanMCF-7 breast cancer cells and A2780 ovarian cancer cells sensitive to anticancer drugs were used. To access the viability of cells, we applied 3-[4,5-dimethylthiazol-2-1]-2,5-diphenyltetrazolium bromide colorimetric assay (MTT-test). Expression of Bcl-2, p-glycoprotein (P-gp), glutathione S-transferase (GST) and E-cadherin was studied by immunocytochemistry. RESULTS: A2780 and MCF-7 cells were treated by homocysteine. It was shown that every next treatment with homocysteine (up to 5th) decreased the sensitivity of A2780 and MCF-7 cells to cytotoxic drugs. Immunocytochemical study of molecular profile of A2780 and MCF-7 cells after long-term cultivation with homocysteine has been carried out and has revealed that such treatment resulted in the induction of Bcl-2, P-gp, GST and E-cadherin expression. This indicates that incubation of studied cells with homocysteine leads to simultaneous induction of expression of drug resistance markers to cisplatin and doxorubicin. CONCLUSION: Cultivation of MCF-7 and A2780 cells with homocysteine leads to simultaneous development of resistance to doxorubicine and cisplatin. The development of drug resistance is diverse for different drugs and varies among cell lines.