Skredėnienė Rūta, Stakišaitis Donatas, Valančiūtė Angelija, Balnytė Ingrida
Department of Histology and Embryology, Medical Academy, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania.
Laboratory of Molecular Oncology, National Cancer Institute, 08660 Vilnius, Lithuania.
Int J Mol Sci. 2025 Jul 15;26(14):6784. doi: 10.3390/ijms26146784.
To date, there is no effective treatment for glioblastoma (GBM). This study aimed to compare the effectiveness of sodium dichloroacetate (NaDCA), a valproic acid and NaDCA combination (VPA-NaDCA), or temozolomide (TMZ) on U87 and T98G cell tumors on the chick embryo chorioallantoic membrane (CAM), and on the expression of proliferating cell nuclear antigen (PCNA), polycomb inhibitory complex catalytic subunit 2 (EZH2), and gene-encoded p53 protein (p53) in tumors on the CAM, and (gene encoding Na-K-2Cl (NKCC1) co-tarnsporter), (gene encoding K-Cl (KCC2) co-transporter), (gene encoding Na-dependent monocarboxylate transporter) and (gene encoding the E-cadherin protein) and (gene encoding the N-cadherin protein) in cells. VPA-NaDCA and TMZ reduced the invasion of U87 and T98G tumors, as well as the expression of PCNA and EZH2 in the tumor. TMZ reduced p53 expression in tumors from both cell lines, whereas VPA-NaDCA did not affect the expression of this marker. VPA-NaDCA, but not TMZ, reduced expression in T98G cells. However, VPA-NaDCA and TMZ did not affect expression in U87 cells. VPA-NaDCA increased expression only in U87 cells, and TMZ did not affect gene expression in either cell line. Only VPA-NaDCA increased expression and decreased expression in T98G cells, whereas TMZ had no effect on gene expression in the study cells. This study demonstrated that VPA-NaDCA exhibits a more effective anticancer effect than NaDCA. The data suggest that VPA-NaDCA has a more effective impact than TMZ; however, the effect of investigational medicines on carcinogenesis varies depending on the cell line. The study of the efficacy of drugs used to treat tumors on the CAM and cells demonstrates that it is essential to assess the effectiveness of treatment, which should be personalized, before administering chemotherapy.
迄今为止，胶质母细胞瘤（GBM）尚无有效的治疗方法。本研究旨在比较二氯乙酸钠（NaDCA）、丙戊酸与NaDCA联合用药（VPA-NaDCA）或替莫唑胺（TMZ）对鸡胚绒毛尿囊膜（CAM）上U87和T98G细胞肿瘤的疗效，以及对CAM上肿瘤中增殖细胞核抗原（PCNA）、多梳抑制复合物催化亚基2（EZH2）和基因编码的p53蛋白（p53）表达的影响，以及对细胞中（编码Na-K-2Cl（NKCC1）共转运体的基因）、（编码K-Cl（KCC2）共转运体的基因）、（编码Na依赖性单羧酸转运体的基因）和（编码E-钙黏蛋白的基因）以及（编码N-钙黏蛋白的基因）表达的影响。VPA-NaDCA和TMZ减少了U87和T98G肿瘤的侵袭，以及肿瘤中PCNA和EZH2的表达。TMZ降低了两种细胞系肿瘤中的p53表达，而VPA-NaDCA不影响该标志物的表达。VPA-NaDCA降低了T98G细胞中的表达，但TMZ没有。然而，VPA-NaDCA和TMZ均未影响U87细胞中的表达。VPA-NaDCA仅增加了U87细胞中的表达，而TMZ对两种细胞系的基因表达均无影响。仅VPA-NaDCA增加了T98G细胞中的表达并降低了表达，而TMZ对研究细胞中的基因表达没有影响。本研究表明，VPA-NaDCA比NaDCA表现出更有效的抗癌作用。数据表明，VPA-NaDCA比TMZ具有更有效的影响；然而，研究药物对致癌作用的影响因细胞系而异。对用于治疗CAM和细胞上肿瘤的药物疗效的研究表明，在进行化疗之前评估治疗效果至关重要，治疗应个性化。
