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https://hdl.handle.net/2440/118348
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Type: | Journal article |
Title: | Methotrexate chemotherapy–induced damages in bone marrow sinusoids: an in vivo and in vitro study |
Author: | Hassanshahi, M. Su, Y.W. Fan, C.M. Khabbazi, S. Hassanshahi, A. Xian, C.J. |
Citation: | Journal of Cellular Biochemistry, 2019; 120(3):3220-3231 |
Publisher: | Wiley |
Issue Date: | 2019 |
ISSN: | 0730-2312 1097-4644 |
Statement of Responsibility: | Mohammadhossein Hassanshahi, Yu‐Wen Su, Chia‐Ming Fan, Samira Khabbazi, Alireza Hassanshahi, Cory J. Xian |
Abstract: | Chemotherapeutic agents are very well evident extrinsic stimuli for causing damage to endothelial cells. Methotrexate is an antimetabolite commonly used to treat solid tumours and paediatric cancers. However, studies on the effect(s) of methotrexate on bone marrow microvascular system are inadequate. In the current study, we observed a significant bone marrow microvascular dilation following methotrexate therapy in rats, accompanied by apoptosis induction in bone marrow sinusoidal endothelial cells, and followed by recovery of bone marrow sinusoids associated with increased proliferation of remaining bone marrow sinusoidal endothelial cells. Our in vitro studies revealed that methotrexate is cytotoxic for cultured sinusoidal endothelial cells and can also induce apoptosis which is associated with upregulation of expression ratio of Bax and Bcl‐2 genes and Bax/Bcl‐2 expression ratio. Furthermore, it was shown that methotrexate can negatively affect proliferation of cultured sinusoidal endothelial cells and also inhibit their abilities of migration and formation of microvessel like tubes. The data from this study indicates that methotrexate can cause significant bone marrow sinusoidal endothelium damage in vivo and induce apoptosis and inhibit proliferation, migration and tube‐forming abilities of sinusoidal endothelial cells in vitro. |
Keywords: | Angiogenesis; apoptosis; bone marrow sinusoidal endothelial cells; bone marrow sinusoids; methotrexate |
Rights: | © 2018 Wiley Periodicals, Inc. |
DOI: | 10.1002/jcb.27589 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1042105 http://purl.org/au-research/grants/nhmrc/1127396 http://purl.org/au-research/grants/nhmrc/508046 http://purl.org/au-research/grants/nhmrc/508047 |
Published version: | http://dx.doi.org/10.1002/jcb.27589 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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