Lukyanova N Yu
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
Exp Oncol. 2010 Mar;32(1):10-4.
To study the influence of homocysteine on the mechanisms of drug resistance formation.
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.
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.
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.
研究同型半胱氨酸对耐药性形成机制的影响。
在本研究中，使用了对抗癌药物敏感的人MCF-7乳腺癌细胞和A2780卵巢癌细胞。为了评估细胞活力，我们应用了3-[4,5-二甲基噻唑-2-1]-2,5-二苯基四氮唑溴盐比色法（MTT试验）。通过免疫细胞化学研究Bcl-2、P-糖蛋白（P-gp）、谷胱甘肽S-转移酶（GST）和E-钙黏蛋白的表达。
用同型半胱氨酸处理A2780和MCF-7细胞。结果表明，每次用同型半胱氨酸处理（直至第5次）都会降低A2780和MCF-7细胞对细胞毒性药物的敏感性。对用同型半胱氨酸长期培养后的A2780和MCF-7细胞的分子谱进行了免疫细胞化学研究，结果显示这种处理导致Bcl-2、P-gp、GST和E-钙黏蛋白表达的诱导。这表明用同型半胱氨酸孵育所研究的细胞会导致对顺铂和阿霉素耐药标志物表达的同时诱导。
用同型半胱氨酸培养MCF-7和A2780细胞会导致对阿霉素和顺铂的耐药性同时产生。不同药物的耐药性发展各不相同，且在不同细胞系之间也有所差异。
