Auranofin induces urothelial carcinoma cell death via reactive oxygen species production and synergy with cisplatin.
Auranofin induces urothelial carcinoma cell death via reactive oxygen species production and synergy with cisplatin.
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DOI：
10.3892/ol.2021.13179
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发表时间：
2022-03
期刊：
影响因子：
2.9
通讯作者：
Fang CY
中科院分区：
文献类型：
--
作者：
Chen SY;Chao CN;Huang HY;Fang CY
尿路上皮癌(UC)是最常见的尿路肿瘤类型之一。UC与较低的5年生存率有关，对以顺铂为基础的治疗耐药仍然是浸润性膀胱癌治疗的挑战。因此，迫切需要开发用于晚期UC治疗的新药。金诺芬(Auranofin，AF)是30多年前开发出来的治疗类风湿性关节炎的药物，据报道，它通过增加癌细胞中的活性氧(ROS)水平来发挥抗肿瘤作用。本研究的目的是研究AF单独或与顺铂联合应用对癌细胞增殖、细胞周期和细胞凋亡的影响。AF通过诱导细胞周期停滞，以浓度和时间依赖的方式诱导两种不同细胞系HT1376和BFTC 909的细胞死亡。但两株细胞周期不同时相的细胞分布不同，HT1376细胞发生G0/G1期阻滞，BFTC909细胞发生S期阻滞。此外，AF还诱导了HT1376细胞的凋亡，以及HT1376和BFTC 909细胞的氧化还原失衡。经ROS清除剂N-乙酰-L-半胱氨酸处理后，细胞活力得以挽救。此外，当AF与顺铂联合治疗时，可协同增加HT1376和BFTC 909细胞的细胞毒作用。这些结果表明，房颤可能是一种潜在的治疗UC的候选药物，并可增加顺铂的治疗效果。
Urothelial carcinoma (UC) is one of the most common cancer types of the urinary tract. UC is associated with poor 5-year survival rate, and resistance to cisplatin-based therapy remains a challenge for invasive bladder cancer treatment. Therefore, there is an urgent need to develop new drugs for advanced UC therapy. Auranofin (AF) was developed over 30 years ago for the treatment of rheumatoid arthritis and has been reported to exert an antitumor effect by increasing the level of reactive oxygen species (ROS) in cancer cells. The aim of the present study was to examine the effects of AF on cancer cell proliferation, cell cycle and apoptosis, either alone or in combination with cisplatin. AF induced cell death in two separate cell lines, HT 1376 and BFTC 909, in a concentration- and time-dependent manner by inducing cell cycle arrest. However, the distribution of cells in different phases of the cell cycle differed between the two cell lines, with G0/G1 cell cycle arrest in HT 1376 cells and S phase arrest in BFTC 909 cells. In addition, AF induced apoptosis in HT 1376, as well as redox imbalance in both HT 1376 and BFTC 909 cells. Cell viability was rescued following treatment with N-acetyl-L-cysteine, a ROS scavenger. Furthermore, AF treatment synergistically increased the cytotoxicity of HT 1376 and BFTC 909 cells when combined with cisplatin treatment. These findings suggest that AF may represent a potential candidate drug against UC and increase the therapeutic effect of cisplatin.
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影响因子：
3.8
作者：
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DOI：
10.1016/j.pbiomolbio.2021.05.002
发表时间：
2021-10
影响因子：
3.8
作者：
Kuczler MD;Olseen AM;Pienta KJ;Amend SR
通讯作者：
Amend SR