尽管化疗取得了重大进展，但由于化疗耐药性，晚期癌症的有效治疗方法在很大程度上仍然难以实现。癌细胞对抗癌药物的耐药性可以通过多种机制产生，包括多重耐药、抑制细胞凋亡、修饰药物靶点以及增强DNA修复能力。因此，迫切需要能够抑制导致耐药性的分子特征的药物。胡椒碱是一种从 Piper nigrum L.（黑胡椒）中提取的活性生物碱，它就是这样一种药物，因其在治疗包括癌症在内的慢性疾病方面的潜力而被广泛研究。胡椒碱的抗肿瘤特性是通过调节众多关键细胞信号通路和调节各种生物过程来介导的。它能够增强药物生物利用度并抵消耐药机制，例如抑制 P-糖蛋白 (P-gp) 和多药耐药相关蛋白 1 (MRP-1)，强调了其作为癌症治疗辅助剂的潜力。针对各种癌症类型的研究已证明胡椒碱通过靶向 P-gp 和 MRP-1 并改变药物代谢酶而在化疗增敏中发挥作用。本综述对胡椒碱的药理学特性及其调节与耐药性相关的多种细胞信号传导途径的能力进行了全面分析。此外，该综述强调了胡椒碱与其他化疗药物或天然化合物联合使用时如何增强治疗效果，从而改善癌症治疗的结果。版权所有 © 2024。由 Elsevier Inc. 出版。

Despite significant advancements in chemotherapy, effective treatments for advanced cancer stages remain largely elusive due to chemoresistance. Resistance to anticancer agents in cancer cells can arise through various mechanisms, including multi-drug resistance, inhibition of apoptosis, modification of drug targets, and enhancement of DNA repair capabilities. Consequently, there is a critical need for agents that can suppress the molecular signatures responsible for drug resistance. Piperine, an active alkaloid extracted from Piper nigrum L. (black pepper), is one such agent that has been extensively studied for its potential in addressing chronic diseases, including cancer. Piperine's antineoplastic properties are mediated through the regulation of numerous key cellular signaling pathways and the modulation of various biological processes. Its capability to enhance drug bioavailability and counteract mechanisms of drug resistance, such as the inhibition of P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP-1), emphasizes its potential as an adjunct in cancer therapy. Research across various cancer types has demonstrated piperine's role in chemosensitization by targeting P-gp and MRP-1 and altering drug-metabolizing enzymes. This review provides a comprehensive analysis of piperine's pharmacological characteristics and its capacity to modulate several cellular signaling pathways involved in drug resistance. Furthermore, the review emphasizes how piperine, when used in conjunction with other chemotherapeutic agents or natural compounds, can enhance therapeutic effects, leading to improved outcomes in cancer treatment.Copyright © 2024. Published by Elsevier Inc.