Chen Chih-I, Chen Yu-Chi, Kao Yi-Kai, Chen Chia-Hung, Yang Po-Wen, Chen Pin-Chun, Song Ling-Chiao, Tsai Kai Lung
Division of Colon and Rectal Surgery, Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan, R.O.C.
School of Medicine for International Students, I-Shou University, Kaohsiung, Taiwan, R.O.C.
Anticancer Res. 2024 Dec;44(12):5371-5378. doi: 10.21873/anticanres.17364.
BACKGROUND/AIM: Irinotecan is a key component of standard first-line treatment for metastatic colorectal cancer. However, irinotecan-induced muscle dysfunction is a contributing factor to cancer cachexia. Here, we present the protective effect of taurine, a conditionally essential amino acid with great antioxidant properties, in attenuating muscle dysfunction induced by irinotecan.
Irinotecan (20 μg/ml) was added to human skeletal muscle cells (HSkMCs) with or without pre-treatment of taurine (5 mM). The effects of taurine and irinotecan on the viability, cytotoxicity, and differentiation ability of HSkMC myoblasts were examined. The intracellular reactive oxygen species (ROS) and endoplasmic reticulum stress (ERS) were also monitored.
Irinotecan caused cytotoxicity of HSkMCs, while taurine pretreatment increased cell viability and inhibited adenylate kinase release significantly in both myoblasts and myotubes. During differentiation, taurine increased ROS clearance and preserved the myotube differentiation ability impaired by irinotecan. Irinotecan exposure resulted in the up-regulation of CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose-regulated protein 78 (GRP78). Taurine pretreatment could combat such irinotecan-induced ERS.
The current in vitro study provides molecular evidence that taurine plays a beneficial role in protecting against irinotecan-induced muscle dysfunction by modulating oxidative stress and endoplasmic reticulum stress.
背景/目的：伊立替康是转移性结直肠癌标准一线治疗的关键组成部分。然而，伊立替康引起的肌肉功能障碍是癌症恶病质的一个促成因素。在此，我们展示了牛磺酸（一种具有强大抗氧化特性的条件必需氨基酸）在减轻伊立替康诱导的肌肉功能障碍方面的保护作用。
将伊立替康（20μg/ml）添加到未预处理或经牛磺酸（5mM）预处理的人骨骼肌细胞（HSkMCs）中。检测牛磺酸和伊立替康对HSkMC成肌细胞的活力、细胞毒性和分化能力的影响。还监测了细胞内活性氧（ROS）和内质网应激（ERS）。
伊立替康导致HSkMCs的细胞毒性，而牛磺酸预处理显著提高了成肌细胞和肌管的细胞活力并抑制了腺苷酸激酶释放。在分化过程中，牛磺酸增加了ROS清除并保留了受伊立替康损害的肌管分化能力。伊立替康暴露导致CCAAT/增强子结合蛋白同源蛋白（CHOP）和葡萄糖调节蛋白78（GRP78）上调。牛磺酸预处理可对抗这种伊立替康诱导的ERS。
目前的体外研究提供了分子证据，表明牛磺酸通过调节氧化应激和内质网应激在预防伊立替康诱导的肌肉功能障碍中发挥有益作用。
