Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran 1477893855, Iran.
Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran 1417466191, Iran.
Molecules. 2021 Apr 19;26(8):2382. doi: 10.3390/molecules26082382.
The failure of chemotherapy is a major challenge nowadays, and in order to ensure effective treatment of cancer patients, it is of great importance to reveal the molecular pathways and mechanisms involved in chemoresistance. Cisplatin (CP) is a platinum-containing drug with anti-tumor activity against different cancers in both pre-clinical and clinical studies. However, drug resistance has restricted its potential in the treatment of cancer patients. CP can promote levels of free radicals, particularly reactive oxygen species (ROS) to induce cell death. Due to the double-edged sword role of ROS in cancer as a pro-survival or pro-death mechanism, ROS can result in CP resistance. In the present review, association of ROS with CP sensitivity/resistance is discussed, and in particular, how molecular pathways, both upstream and downstream targets, can affect the response of cancer cells to CP chemotherapy. Furthermore, anti-tumor compounds, such as curcumin, emodin, chloroquine that regulate ROS and related molecular pathways in increasing CP sensitivity are described. Nanoparticles can provide co-delivery of CP with anti-tumor agents and by mediating photodynamic therapy, and induce ROS overgeneration to trigger CP sensitivity. Genetic tools, such as small interfering RNA (siRNA) can down-regulate molecular pathways such as HIF-1α and Nrf2 to promote ROS levels, leading to CP sensitivity. Considering the relationship between ROS and CP chemotherapy, and translating these findings to clinic can pave the way for effective treatment of cancer patients.
化疗失败是当今面临的主要挑战，为了确保癌症患者的有效治疗，揭示化疗耐药相关的分子途径和机制非常重要。顺铂（CP）是一种含铂药物，在临床前和临床研究中对不同癌症均具有抗肿瘤活性。然而，耐药性限制了其在癌症患者治疗中的潜力。CP 可促进自由基水平，特别是活性氧（ROS）的产生，从而诱导细胞死亡。由于 ROS 在癌症中的双重作用，作为一种生存或死亡机制，ROS 可导致 CP 耐药。本综述讨论了 ROS 与 CP 敏感性/耐药性的关联，特别是上游和下游靶点的分子途径如何影响癌细胞对 CP 化疗的反应。此外，还描述了一些能够调节 ROS 及相关分子途径，从而提高 CP 敏感性的抗肿瘤化合物，如姜黄素、大黄素、氯喹。纳米颗粒可以提供 CP 与抗肿瘤药物的共递药，并通过介导光动力疗法，引发 ROS 的过度产生，从而引发 CP 敏感性。遗传工具，如小干扰 RNA（siRNA），可以下调 HIF-1α 和 Nrf2 等分子途径，从而提高 ROS 水平，导致 CP 敏感性。考虑到 ROS 与 CP 化疗之间的关系，并将这些发现转化为临床应用，可以为癌症患者的有效治疗铺平道路。
