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砷化合物在非小细胞肺癌中的抗癌作用

Anticancer Effects of Arsenic Compounds in Non-Small Cell Lung Cancer.

作者信息

Konduri Neelima, Thyagarajan Anita, Sahu Ravi P

机构信息

Department of Pharmacology and Toxicology, Boonshoft School of Medicine Wright State University, Dayton, OH 45435, USA.

出版信息

Dis Res. 2024 Dec;4(2):87-96. doi: 10.54457/dr.202402003. Epub 2024 Sep 20.

Abstract

Non-small cell lung cancer (NSCLC) is the most common and prevalent subtype of lung cancer and continues to be one of the leading causes of cancer-related deaths worldwide. Despite various treatment options, a majority of NSCLC patients continue to experience disease progression and associated side effects, which are largely attributed to drug resistance, indicating the need for alternative strategies to combat this deadly disease. Among various applicable alternative approaches, repurposed drugs such as arsenic compounds have been shown to exert anticarcinogenic properties against NSCLC and possess the ability to overcome drug resistance mechanisms. Notably, numerous studies have demonstrated that the antitumor effects of arsenic compounds such as arsenic trioxide, arsenic sulfide, and tetra arsenic hexoxide are mediated via their ability to target several oncogenic signaling pathways, including nuclear factor-kappa B (NF-kB), epidermal growth factor receptor (EGFR), and signal transducer and activator of transcription 3 (STAT3). Inhibition of such signaling cascades results in altered cellular activities, including cell cycle arrest, decreased proliferation, and increased apoptosis. Importantly, these arsenic compounds have also been shown to overcome tumor resistance mechanisms and/or exert synergy in combination with other therapeutic agents resulting in the augmentation of cancer cell cytotoxicity. This review highlights the anticarcinogenic mechanisms of arsenic compounds and their impact on the efficacy of therapeutic agents.

摘要

非小细胞肺癌(NSCLC)是肺癌最常见且普遍的亚型,并且仍然是全球癌症相关死亡的主要原因之一。尽管有多种治疗选择,但大多数NSCLC患者仍会经历疾病进展及相关副作用,这在很大程度上归因于耐药性,这表明需要采用替代策略来对抗这种致命疾病。在各种适用的替代方法中,如砷化合物等重新利用的药物已显示出对NSCLC具有抗癌特性,并具有克服耐药机制的能力。值得注意的是,大量研究表明,三氧化二砷、硫化砷和四氧化六砷等砷化合物的抗肿瘤作用是通过它们靶向几种致癌信号通路的能力介导的,这些信号通路包括核因子-κB(NF-κB)、表皮生长因子受体(EGFR)和信号转导子及转录激活子3(STAT3)。抑制这些信号级联反应会导致细胞活动改变,包括细胞周期停滞、增殖减少和细胞凋亡增加。重要的是,这些砷化合物还被证明能克服肿瘤耐药机制和/或与其他治疗药物联合发挥协同作用,从而增强癌细胞的细胞毒性。本综述重点介绍了砷化合物的抗癌机制及其对治疗药物疗效的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb3/11666069/0464e49bcd28/nihms-2024722-f0001.jpg

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