顺铂是最常用的癌症治疗药物之一。尽管在改善患者预后方面取得了很大进展，但许多患者对基于顺铂的治疗有抵抗力，导致治疗效果有限并增加治疗失败。几十年来，实体瘤遭受肿瘤微环境缺氧和血液供应不足的事实已被广泛接受。大量研究表明，缺氧微环境显着降低肿瘤细胞对顺铂的敏感性。因此，了解缺氧如何使肿瘤细胞产生顺铂耐药性至关重要。在对抗肿瘤的斗争中，开发克服耐药性的创新策略引起了广泛的兴趣。天然产物因其明显的功效和丰富的候选资源，历来为抗癌药物研究做出了重大贡献。有趣的是，天然产物显示出逆转化疗耐药性的潜力，这为缺氧肿瘤微环境中的顺铂耐药性提供了新的见解。在这篇综述中，我们描述了顺铂在肿瘤治疗中的作用以及肿瘤细胞产生顺铂耐药性的机制。随后，我们提请注意缺氧微环境与顺铂耐药之间的联系。此外，我们总结了针对缺氧肿瘤微环境以克服顺铂耐药性的已知和潜在的天然产物。最后，我们讨论了当前限制天然产物临床应用的挑战。了解缺氧与顺铂耐药性之间的联系是释放天然产物全部潜力的关键，天然产物将成为能够克服耐药性的新治疗策略。版权所有 © 2024。由 Elsevier B.V. 出版。

Cisplatin is one of the most commonly used drugs for cancer treatment. Despite much progress in improving patient outcomes, many patients are resistant to cisplatin-based treatments, leading to limited treatment efficacy and increased treatment failure. The fact that solid tumors suffer from hypoxia and an inadequate blood supply in the tumor microenvironment has been widely accepted for decades. Numerous studies have shown that a hypoxic microenvironment significantly reduces the sensitivity of tumor cells to cisplatin. Therefore, understanding how hypoxia empowers tumor cells with cisplatin resistance is essential. In the fight against tumors, developing innovative strategies for overcoming drug resistance has attracted widespread interest. Natural products have historically made major contributions to anticancer drug research due to their obvious efficacy and abundant candidate resources. Intriguingly, natural products show the potential to reverse chemoresistance, which provides new insights into cisplatin resistance in the hypoxic tumor microenvironment. In this review, we describe the role of cisplatin in tumor therapy and the mechanisms by which tumor cells generate cisplatin resistance. Subsequently, we call attention to the linkage between the hypoxic microenvironment and cisplatin resistance. Furthermore, we summarize known and potential natural products that target the hypoxic tumor microenvironment to overcome cisplatin resistance. Finally, we discuss the current challenges that limit the clinical application of natural products. Understanding the link between hypoxia and cisplatin resistance is the key to unlocking the full potential of natural products, which will serve as new therapeutic strategies capable of overcoming resistance.Copyright © 2024. Published by Elsevier B.V.