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STAT3 磷酸化抑制剂 Bt354 对多形性胶质母细胞瘤细胞具有抗肿瘤活性。

STAT3 phosphorylation inhibitor Bt354 exhibits anti-neoplastic activity in glioblastoma multiforme cells.

机构信息

Department of Surgery, Division of Neurosurgery, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan.

Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung, Taiwan.

出版信息

Environ Toxicol. 2024 Jun;39(6):3292-3303. doi: 10.1002/tox.24178. Epub 2024 Feb 28.

Abstract

The high mortality rate of glioblastoma multiforme (GBM), a lethal primary brain tumor, is attributable to postsurgical recurrence. STAT3, an oncogenic protein, is a signal transducer and transcription activator encourages cancer cell migration and proliferation, which results in resistance to therapy. STAT3 inhibition reduces cancer metastasis and improves patient prognosis. Bt354, a small molecule STAT inhibitor, exhibits significant cytotoxic and anti-proliferative activities against certain cancer types. Here, we demonstrated that exposure of GBM cells (U87 MG) to Bt354 had a significant, concentration-dependent growth suppression. Bt354 also induced apoptosis and downregulated the expression of the epithelial-mesenchymal transition genes. Therefore, this study suggests the potential of Bt354 for treating GBM owing to its ability to induce cytotoxicity.

摘要

多形性胶质母细胞瘤(GBM)是一种致命的原发性脑肿瘤,其高死亡率归因于手术后的复发。STAT3 是一种致癌蛋白,作为信号转导和转录激活因子,促进癌细胞的迁移和增殖,从而导致对治疗的耐药性。STAT3 抑制可减少癌症转移并改善患者预后。小分子 STAT 抑制剂 Bt354 对某些癌症类型具有显著的细胞毒性和抗增殖活性。在这里,我们证明了 Bt354 暴露于 GBM 细胞(U87 MG)可显著抑制浓度依赖性生长。Bt354 还诱导细胞凋亡并下调上皮-间充质转化基因的表达。因此,由于其诱导细胞毒性的能力,本研究表明 Bt354 有治疗 GBM 的潜力。

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