胃癌類白金抗藥性的分子機制和藥理干預/納米治療的最新研究狀況。
A state-of-art of underlying molecular mechanisms and pharmacological interventions/nanotherapeutics for cisplatin resistance in gastric cancer.
发表日期：2023 Aug 31
作者：
Jitendra Gupta, Abdulrahman T Ahmed, Nahla A Tayyib, Rahman S Zabibah, Qakhramon Shomurodov, Mostafai N Kadheim, Fahad Alsaikhan, Pushpamala Ramaiah, Lathamangeswari Chinnasamy, Saeed Samarghandian
来源：
Cell Death & Disease
摘要：
胃癌 (GC) 是患者死亡的第四个常见原因，而且在东亚地区是一种主要的肿瘤类型。胃癌治疗中的一个问题是化疗抵抗。顺铂 (CP) 是一种铂化合物，通过引起 DNA 损伤来减少肿瘤进展和癌细胞的存活能力。然而，由于药物外排泵的高活性、基因失调和肿瘤微环境中的相互作用，肿瘤细胞可以对 CP 化疗产生抵抗性。此次综述侧重于胃癌细胞中 CP 抵抗性的出现，着重讨论分子途径、逆转化疗抵抗性的药物化合物和纳米结构的作用。细胞死亡机制的改变，如刺激细胞自噬的上调，可以阻止 CP 介导的凋亡，从而导致药物抵抗性。此外，通过诱导 EMT 增加转移的，在诱导 CP 抵抗性方面起到作用。PTEN、PI3K/Akt、Nrf2 等分子途径的失调会导致 GC 细胞对 CP 反应的改变。非编码 RNA 决定胃癌细胞对 CP 的反应，而应用具有与 CP 不同活性的药物化合物可以增强肿瘤细胞的敏感性。由于外泌体在胃癌细胞之间传递 RNA 和 DNA 等生物活性分子的有效性，外泌体也可能导致 CP 抵抗性。在克服胃癌中 CP 抵抗性方面的最新进展之一是应用纳米平台来输送 CP 进行胃癌治疗，它们可以增加 CP 在肿瘤部位的积累，并通过抑制致癌因子和克服生物屏障来增加对癌细胞的毒性。版权©2023。由 Elsevier Masson SAS 出版。
The fourth common reason of death among patients is gastric cancer (GC) and it is a dominant tumor type in Ease Asia. One of the problems in GC therapy is chemoresistance. Cisplatin (CP) is a platinum compound that causes DNA damage in reducing tumor progression and viability of cancer cells. However, due to hyperactivation of drug efflux pumps, dysregulation of genes and interactions in tumor microenvironment, tumor cells can develop resistance to CP chemotherapy. The current review focuses on the CP resistance emergence in GC cells with emphasizing on molecular pathways, pharmacological compounds for reversing chemoresistance and the role of nanostructures. Changes in cell death mechanisms such as upregulation of pro-survival autophagy can prevent CP-mediated apoptosis that results in drug resistance. Moreover, increase in metastasis via EMT induction induces CP resistance. Dysregulation of molecular pathways such as PTEN, PI3K/Akt, Nrf2 and others result in changes in CP response of GC cells. Non-coding RNAs determine CP response of GC cells and application of pharmacological compounds with activity distinct of CP can result in sensitivity in tumor cells. Due to efficacy of exosomes in transferring bioactive molecules such as RNA and DNA molecules among GC cells, exosomes can also result in CP resistance. One of the newest progresses in overcoming CP resistance in GC is application of nanoplatforms for delivery of CP in GC therapy that they can increase accumulation of CP at tumor site and by suppressing carcinogenic factors and overcoming biological barriers, they increase CP toxicity on cancer cells.Copyright © 2023. Published by Elsevier Masson SAS.