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Calpain is involved in cisplatin-induced endothelial injury in an in vitro three-dimensional blood vessel model

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To study endothelial injury in vitro, we established a three-dimensional (3-D) blood vessel model in which human umbilical vein endothelial cells were grown in the presence of basic fibroblast growth factor and vascular endothelial growth factor. We then performed comparative studies on cisplatin (cis-platinum-diammine-dichloride, CDDP)-induced endothelial injury in 3-D and monolayer cultures. In 3-D culture, CDDP induced cell death and tube breakdown without DNA damage, whereas CDDP induced apoptosis accompanied by DNA damage in monolayer culture. CDDP also induced caspase-3 activation in a concentration-dependent manner in both cultures. A broad-spectrum caspase inhibitor, zVAD-fmk, failed to prevent CDDP-induced cell death and tube breakdown in 3-D culture, whereas zVAD-fmk suppressed CDDP-induced apoptosis in monolayer culture. A calpain inhibitor, MDL28170, attenuated CDDP-induced cell death and tube breakdown in 3-D culture, but not apoptosis in monolayer culture. These results showed that calpain is involved in CDDP-induced endothelial injury in 3-D culture and there are significant differences in signaling pathways between 3-D and monolayer cultures.
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Document Type: Research Article

Affiliations: Department of Thoracic Oncology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan

Publication date: November 1, 2010

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  • The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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