Department of Surgery, University Hospital of Giessen and Marburg, Philipps-University of Marburg, Marburg, Germany.
J Surg Oncol. 2012 Mar 15;105(4):357-64. doi: 10.1002/jso.22113. Epub 2011 Oct 17.
Targeting the ubiquitin-proteasome system by using proteasome inhibitors represents a novel approach for cancer therapy. Anaplastic thyroid cancer (ATC), a subtype of thyroid cancer (TC), fails to respond to conventional TC treatment. Here we investigated the effects of bortezomib on TC in vitro. Further, the study aimed to evaluate its potential for TC treatment in vivo.
Three anaplastic (Hth74, C643, Kat4), one follicular (FTC133), and one papillary (TPC1) TC cell lines were used. Antiproliferative, proapoptotic, and transcriptional effects of bortezomib treatment were analyzed in vitro and growth inhibition of ATC xenografts in vivo. Tumor samples were analyzed by Ki67, CD31, caspase-3, and NF-κB immunohistochemistry.
In vitro, bortezomib inhibited proliferation of TC cells (IC(50) 4-10 nM), increased caspase-3 activity and induced cell cycle arrest. NF-κB activity was affected differently. In vivo, bortezomib treatment was effective in reducing tumor volume (up to 74%), accompanied by reduced proliferation (Ki67) and 57% reduced tumor vascularity.
Proteasome inhibition is effective in reducing cell growth and inducing apoptosis of ATC in vitro and inhibiting tumor growth and vascularity in vivo. However, the impact on nuclear transcription remains controversial. Clinical evaluation of bortezomib treatment in ATC is warranted.
利用蛋白酶体抑制剂靶向泛素-蛋白酶体系统是癌症治疗的一种新方法。间变性甲状腺癌（ATC）是甲状腺癌（TC）的一种亚型，对常规 TC 治疗无反应。本研究旨在探讨硼替佐米对 TC 的体外作用，并评估其在体内治疗 TC 的潜力。
使用三种间变性（Hth74、C643、Kat4）、一种滤泡性（FTC133）和一种乳头状（TPC1）TC 细胞系。分析硼替佐米处理的体外抗增殖、促凋亡和转录效应，以及 ATC 异种移植物的体内生长抑制作用。Ki67、CD31、caspase-3 和 NF-κB 免疫组织化学分析肿瘤样本。
体外，硼替佐米抑制 TC 细胞增殖（IC50 为 4-10 nM），增加 caspase-3 活性并诱导细胞周期停滞。NF-κB 活性受到不同影响。体内，硼替佐米治疗有效降低肿瘤体积（高达 74%），同时降低增殖（Ki67）和肿瘤血管生成减少 57%。
蛋白酶体抑制在体外有效减少 ATC 细胞生长和诱导细胞凋亡，并在体内抑制肿瘤生长和血管生成。然而，对核转录的影响仍存在争议。需要对 ATC 的硼替佐米治疗进行临床评估。
