Damanskienė Eligija, Balnytė Ingrida, Valančiūtė Angelija, Alonso Marta Maria, Preikšaitis Aidanas, Stakišaitis Donatas
Department of Histology and Embryology, Medical Academy, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania.
Department of Pediatrics, Clínica Universidad de Navarra, University of Navarra, 31008 Pamplona, Spain.
Int J Mol Sci. 2022 Feb 11;23(4):2001. doi: 10.3390/ijms23042001.
It is necessary to elucidate the individual effects of temozolomide (TMZ) on carcinogenesis and tumor resistance to chemotherapy mechanisms. The study aimed to investigate the TMZ 50 and 100 μM dose effect difference between PBT24 and SF8628 cell line high-grade pediatric glioblastoma (phGBM) xenografts in a chicken chorioallantoic membrane (CAM) model, on PCNA and EZH2 immunohistochemical expression in the tumor and on the expression of NKCC1, KCC2, E- and N-cadherin genes in TMZ-treated and control cell groups in vitro. TMZ at a 100 μg dose reduced the incidence of PBT24 xenograft invasion into the CAM, CAM thickening and the number of blood vessels in the CAM ( < 0.05), but did not affect the SF8628 tumor in the CAM model. The TMZ impact on PBT24 and SF8628 tumor PCNA expression was similarly significantly effective but did not alter EZH2 expression in the studied tumors. The TMZ at 50 μM caused significantly increased RNA expression of the NKCC1 gene in both studied cell types compared with controls ( < 0.05). The expression of the KCC2 gene was increased in PBT24 TMZ-treated cells ( < 0.05), and no TMZ effect was found in SF8628-treated cells. The study supports the suggestion that individual sensitivity to TMZ should be assessed when starting treatment.
有必要阐明替莫唑胺（TMZ）对肿瘤发生和肿瘤化疗耐药机制的个体影响。本研究旨在探讨在鸡胚绒毛尿囊膜（CAM）模型中，PBT24和SF8628细胞系的高级别小儿胶质母细胞瘤（phGBM）异种移植瘤中，TMZ 50和100 μM剂量效应差异，对肿瘤中增殖细胞核抗原（PCNA）和EZH2免疫组化表达的影响，以及对体外TMZ处理组和对照组细胞中NKCC1、KCC2、E-钙黏蛋白和N-钙黏蛋白基因表达的影响。100 μg剂量的TMZ降低了PBT24异种移植瘤侵袭CAM的发生率、CAM增厚以及CAM中的血管数量（P<0.05），但在CAM模型中对SF8628肿瘤无影响。TMZ对PBT24和SF8628肿瘤PCNA表达的影响同样显著有效，但未改变所研究肿瘤中EZH2的表达。与对照组相比，50 μM的TMZ使两种研究细胞类型中NKCC1基因的RNA表达均显著增加（P<0.05）。PBT24经TMZ处理的细胞中KCC2基因表达增加（P<0.05），而SF8628经处理的细胞中未发现TMZ效应。该研究支持在开始治疗时应评估个体对TMZ敏感性的建议。
