Department of Orthopedic Surgery, Chiba Cancer Center, Chiba, Japan;
Laboratory of Oncogenomics, Chiba Cancer Center Research Institute, Chiba, Japan.
Anticancer Res. 2021 Dec;41(12):6013-6021. doi: 10.21873/anticanres.15420.
BACKGROUND/AIM: The thioredoxin-1 (Trx-1) inhibitor, PX-12, is active against several cancer types. This study aimed to evaluate its effects on local osteosarcoma (OS) progression and to describe PX-12-related signal transduction pathways.
Publicly available expression cohort data were analyzed to determine the relationship between the expression levels of TXN, which codes for the Trx protein, and survival in patients with OS. Murine LM8 OS cells were stimulated with PX-12. Apoptosis-related protein levels, cell viability, caspase activity, and wound healing were evaluated. PX-12 efficacy in suppressing tumor progression was evaluated in C3H mice injected with LM8 cells.
High TXN expression was a negative prognostic factor for metastasis and overall survival in OS patients. PX-12 induced apoptosis in OS cells via the oxidative stress-MAPK-caspase 3 pathway and suppressed OS cell migration. PX-12 suppressed local OS progression.
PX-12 is a potential therapeutic agent for use in suppressing local OS progression.
背景/目的：硫氧还蛋白-1（Trx-1）抑制剂 PX-12 对多种癌症类型具有活性。本研究旨在评估其对局部骨肉瘤（OS）进展的影响，并描述 PX-12 相关的信号转导途径。
分析公开可用的表达队列数据，以确定编码 Trx 蛋白的 TXN 的表达水平与 OS 患者生存之间的关系。用 PX-12 刺激小鼠 LM8 OS 细胞。评估凋亡相关蛋白水平、细胞活力、半胱天冬酶活性和伤口愈合。用 LM8 细胞注射 C3H 小鼠来评估 PX-12 抑制肿瘤进展的功效。
高 TXN 表达是 OS 患者转移和总生存的负预后因素。PX-12 通过氧化应激-MAPK-半胱天冬酶 3 途径诱导 OS 细胞凋亡，并抑制 OS 细胞迁移。PX-12 抑制局部 OS 进展。
PX-12 是一种潜在的治疗剂，可用于抑制局部 OS 进展。
