替莫唑胺
胶质瘤
生物物理学
流式细胞术
细胞毒性
化学
癌细胞
材料科学
癌症研究
细胞生物学
生物医学工程
生物
体外
生物化学
医学
癌症
免疫学
内科学
作者
Mateusz Cieśluk,Ewelina Piktel,Urszula Wnorowska,Karol Skłodowski,Jan Kochanowicz,Alina Kułakowska,Robert Bucki,Katarzyna Pogoda
标识
DOI:10.1016/j.bbadis.2022.166513
摘要
The mechanical state of the extracellular environment of the brain cells considerably affects their phenotype during the development of central nervous system (CNS) pathologies, and when the cells respond to drugs. The reports on the evaluation of the viscoelastic properties of different brain tumors have shown that both tissue stiffness and viscosity can be altered during cancer development. Although a compelling number of reports established the role of substrate stiffness on the proliferation, motility, and drug sensitivity of brain cancer cells, there is a lack of parallel data in terms of alterations in substrate viscosity.Based on viscoelasticity measurements of rat brain samples using strain rheometry, polyacrylamide (PAA) hydrogels mimicking elastic and viscous parameters of the tissues were prepared. Optical microscopy and flow cytometry were employed to assess the differences in glioblastoma cells morphology, proliferation, and cytotoxicity of anticancer drug temozolomide (TMZ) due to increased substrate viscosity.Our results indicate that changes in substrate viscosity affect the proliferation of untreated glioma cells to a lesser extent, but have a significant impact on the apoptosis-associated depolarization of mitochondria and level of DNA fragmentation. This suggests that viscosity sensing and stiffness sensing machinery can activate different signaling pathways in glioma cells.Collected data indicate that viscosity should be considered an important parameter in in vitro polymer-based cell culture systems used for drug screening.
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