Methotrexate chemotherapy–induced damages in bone marrow sinusoids: an in vivo and in vitro study

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dc.contributor.authorHassanshahi, M.
dc.contributor.authorSu, Y.W.
dc.contributor.authorFan, C.M.
dc.contributor.authorKhabbazi, S.
dc.contributor.authorHassanshahi, A.
dc.contributor.authorXian, C.J.
dc.date.issued2019
dc.description.abstractChemotherapeutic 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.
dc.description.statementofresponsibilityMohammadhossein Hassanshahi, Yu‐Wen Su, Chia‐Ming Fan, Samira Khabbazi, Alireza Hassanshahi, Cory J. Xian
dc.identifier.citationJournal of Cellular Biochemistry, 2019; 120(3):3220-3231
dc.identifier.doi10.1002/jcb.27589
dc.identifier.issn0730-2312
dc.identifier.issn1097-4644
dc.identifier.orcidHassanshahi, M. [0000-0002-4097-8527]
dc.identifier.orcidKhabbazi, S. [0000-0002-5410-795X]
dc.identifier.orcidXian, C.J. [0000-0002-8467-2845]
dc.identifier.urihttp://hdl.handle.net/2440/118348
dc.language.isoen
dc.publisherWiley
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1042105
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1127396
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/508046
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/508047
dc.rights© 2018 Wiley Periodicals, Inc.
dc.source.urihttps://doi.org/10.1002/jcb.27589
dc.subjectAngiogenesis; apoptosis; bone marrow sinusoidal endothelial cells; bone marrow sinusoids; methotrexate
dc.titleMethotrexate chemotherapy–induced damages in bone marrow sinusoids: an in vivo and in vitro study
dc.typeJournal article
pubs.publication-statusPublished

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