间皮瘤
阿霉素
细胞凋亡
癌症研究
氧化应激
化疗
间皮细胞
病理
化学
生物
医学
内科学
生物化学
作者
Gustav Nilsonne,Xiaojuan Sun,Christina Nyström,Anna-Klara Rundlöf,Aristi P. Fernandes,Mikael Björnstedt,Katalin Dobra
标识
DOI:10.1016/j.freeradbiomed.2006.04.031
摘要
Malignant mesothelioma cells differentiate into sarcomatoid or epithelioid phenotypes. The sarcomatoid cell type is more resistant to chemotherapy and gives a worse prognosis. We have investigated whether selenite alone and in combination with doxorubicin induced apoptosis in variously differentiated mesothelioma cells. Selenite in concentrations that could potentially be administered to patients strongly inhibited the growth of the sarcomatoid mesothelioma cells (IC50 = 7.5 μM), whereas epithelioid cells were more sensitive to doxorubicin. Benign mesothelial cells remained largely unaffected. Selenite potentiated doxorubicin treatment. Apoptosis was the dominating mode of cell death. The toxicity of selenite was mediated by oxidative stress. Furthermore the activity of the thioredoxin system was directly dependent on the concentration of selenite. This offers a possible mechanism of action of selenite treatment. Our findings suggest that selenite is a promising new drug for the treatment of malignant mesothelioma.
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