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达克罗宁增强蛋白酶体抑制剂硼替佐米对多发性骨髓瘤细胞的细胞毒性作用。

Dyclonine enhances the cytotoxic effect of proteasome inhibitor bortezomib in multiple myeloma cells.

作者信息

Ju Donghong, Xie Youming

机构信息

Karmanos Cancer Institute, Department of Oncology and Pathology, Wayne State University School of Medicine, Detroit, MI 48201, USA.

出版信息

Mol Med Rep. 2014 Nov;10(5):2609-12. doi: 10.3892/mmr.2014.2522. Epub 2014 Aug 28.

Abstract

The proteasome has become an important target for cancer therapy with the approval of bortezomib for the treatment of relapsed/refractory multiple myeloma (MM). However, numerous patients with MM do not respond to bortezomib and those responding initially often acquire resistance. Recent clinical studies have also demonstrated that bortezomib is also inefficacious in the treatment of other types of cancer. Therefore, it is imperative to develop novel approaches and agents for proteasome-targeting cancer therapy. In the present study, it was revealed that dyclonine, a major component of the cough droplets Sucrets, markedly enhances the cytotoxic effects of bortezomib and minimizes drug resistance in MM cells. It was demonstrated that a combination of bortezomib and dyclonine markedly induced apoptosis of MM cells. The present study suggests a novel therapeutic use of an over‑the‑counter medicine for the treatment of MM.

摘要

随着硼替佐米被批准用于治疗复发/难治性多发性骨髓瘤(MM),蛋白酶体已成为癌症治疗的一个重要靶点。然而,许多MM患者对硼替佐米无反应,而那些最初有反应的患者往往会产生耐药性。最近的临床研究还表明,硼替佐米在治疗其他类型癌症方面也无效。因此,开发针对蛋白酶体的癌症治疗新方法和药物势在必行。在本研究中,发现咳嗽糖浆Sucrets的主要成分达克罗宁可显著增强硼替佐米的细胞毒性作用,并使MM细胞中的耐药性降至最低。结果表明,硼替佐米与达克罗宁联合使用可显著诱导MM细胞凋亡。本研究提示了一种非处方药在MM治疗中的新治疗用途。

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