曲妥珠单抗（Tz）和硒-曲妥珠单抗（Se-Tz）对 Her/2 乳腺癌细胞系 JIMT-1 和 BT-474 的体外细胞毒性。

In Vitro Cytotoxicity of Trastuzumab (Tz) and Se-Trastuzumab (Se-Tz) against the Her/2 Breast Cancer Cell Lines JIMT-1 and BT-474.

机构信息

Nutritional Sciences, College of Human Sciences, Texas Tech University, Lubbock, TX 79409, USA.

Department of Pharmacology, Penn State Cancer Institute, CH72, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.

出版信息

Int J Mol Sci. 2021 Apr 28;22(9):4655. doi: 10.3390/ijms22094655.

DOI:10.3390/ijms22094655

PMID:33925081

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8124313/

Abstract

Her/2+ breast cancer accounts for ~25% mortality in women and overexpression of Her/2 leads to cell growth and tumor progression. Trastuzumab (Tz) with Taxane is the preferred treatment for Her/2+ patients. However, Tz responsive patients often develop resistance to Tz treatment. Herein, redox selenides (RSe-) were covalently linked to Tz using a selenium (Se)-modified Bolton-Hunter Reagent forming Seleno-Trastuzumab (Se-Tz; ~25 µgSe/mg). Se-Tz was compared to Tz and sodium selenite to assess the viability of JIMT-1 and BT-474 cells. Comparative cell viability was examined by microscopy and assessed by fluorometric/enzymatic assays. Se-Tz and selenite redox cycle producing superoxide (O) are more cytotoxic to Tz resistant JIMT-1 and Tz sensitive BT-474 cells than Tz. The results of conjugating redox selenides to Tz suggest a wider application of this technology to other antibodies and targeting molecules.

摘要

Her/2+ 乳腺癌占女性死亡率的25%，Her/2 的过表达导致细胞生长和肿瘤进展。曲妥珠单抗（Tz）联合紫杉烷类药物是 Her/2+ 患者的首选治疗方法。然而，Tz 反应性患者常对 Tz 治疗产生耐药性。在此，使用硒（Se）修饰的 Bolton-Hunter 试剂将氧化还原硒化物（RSe-）共价连接到 Tz 上，形成硒代曲妥珠单抗（Se-Tz；25 µgSe/mg）。将 Se-Tz 与 Tz 和亚硒酸钠进行比较，以评估 JIMT-1 和 BT-474 细胞的活力。通过显微镜检查和荧光酶标法评估来比较细胞活力。与 Tz 相比，Se-Tz 和亚硒酸钠氧化还原循环产生的超氧阴离子（O）对 Tz 耐药的 JIMT-1 和 Tz 敏感的 BT-474 细胞更具细胞毒性。将氧化还原硒化物与 Tz 偶联的结果表明，该技术在其他抗体和靶向分子中有更广泛的应用。