评价端粒酶抑制剂 BIBR1532 在甲状腺未分化癌中的抗癌作用，从凋亡、迁移和细胞周期方面。
Evaluation of the anticancer effect of telomerase inhibitor BIBR1532 in anaplastic thyroid cancer in terms of apoptosis, migration and cell cycle.
机构信息
Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey.
Department of Endocrinology and Metabolism, Faculty of Medicine, Ege University, Izmir, Turkey.
出版信息
Med Oncol. 2023 Jun 7;40(7):196. doi: 10.1007/s12032-023-02063-0.
Anaplastic thyroid cancer (ATC) represents the type with the worst prognosis among thyroid cancers. In ATC with a highly invasive phenotype, selective targeting of TERT with BIBR1532 may be a goal-driven approach to preserving healthy tissues. In present study, it was aimed to investigate the effects of treatment of SW1736 cells with BIBR1532 on apoptosis, cell cycle progression, and migration. The apoptotic effect of BIBR1532 on SW1736 cells was examined using the Annexin V method, the cytostatic effect using cell cycle test, migration properties using wound healing assay. Gene expression differences were determined by real-time qRT-PCR and differences in protein level by ELISA test. BIBR1532-treated SW1736 cells had 3.1-fold increase in apoptosis compared to their untreated counterpart. There was 58.1% arrest in the G/G phase and 27.6% arrest in the S phase of the cell cycle in untreated group, treatment with BIBR1532 increased cell population in G/G phase to 80.9% and decreased in S phase to 7.1%. Treatment with the TERT inhibitor resulted in a 50.8% decrease in cell migration compared to the untreated group. After BIBR1532 treatment of SW1736 cells, upregulation of BAD, BAX, CASP8, CYCS, TNFSF10, CDKN2A genes, and downregulation of BCL2L11, XIAP, CCND2 genes were detected. BIBR1532 treatment resulted in an increase in BAX and p16 proteins, and a decrease in concentration of BCL-2 protein compared to untreated group. Targeting TERT with BIBR1532 as a mono drug or using of BIBR1532 at "priming stage" prior to chemotherapy treatment in ATC may present a novel and promising treatment strategy.
间变性甲状腺癌（ATC）是甲状腺癌中预后最差的类型。在具有高度侵袭性表型的 ATC 中，用 BIBR1532 选择性靶向 TERT 可能是一种保留健康组织的靶向治疗方法。在本研究中，旨在研究用 BIBR1532 治疗 SW1736 细胞对细胞凋亡、细胞周期进展和迁移的影响。用 Annexin V 法检测 BIBR1532 对 SW1736 细胞的凋亡作用，用细胞周期试验检测细胞生长抑制作用，用划痕愈合试验检测迁移特性。用实时 qRT-PCR 测定基因表达差异，用 ELISA 试验测定蛋白水平差异。与未处理的对照相比，BIBR1532 处理的 SW1736 细胞凋亡增加了 3.1 倍。未处理组的细胞周期中 G/G 期有 58.1%的阻滞，S 期有 27.6%的阻滞，用 BIBR1532 处理后，G/G 期的细胞群体增加到 80.9%，S 期减少到 7.1%。与未处理组相比，用 TERT 抑制剂处理导致细胞迁移减少 50.8%。用 BIBR1532 处理 SW1736 细胞后，BAD、BAX、CASP8、CYCS、TNFSF10、CDKN2A 基因上调，BCL2L11、XIAP、CCND2 基因下调。与未处理组相比，BIBR1532 处理后 BAX 和 p16 蛋白增加，BCL-2 蛋白浓度降低。用 BIBR1532 作为单药靶向 TERT，或在 ATC 化疗前的“启动阶段”使用 BIBR1532，可能是一种新的有前途的治疗策略。
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