Ni Xuan, Li Li, Pan Guoyu
Center for Drug Safety Evaluation and Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P.R. China.
Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993-0002, USA.
Oncol Lett. 2015 Feb;9(2):515-521. doi: 10.3892/ol.2014.2714. Epub 2014 Nov 19.
Histone deacetylase (HDAC) inhibitors are becoming a novel and promising class of antineoplastic agents that have been used for cancer therapy in the clinic. Two HDAC inhibitors, vorinostat and romidepsin, have been approved by the Food and Drug Administration to treat T-cell lymphoma. Nevertheless, similar to common anticancer drugs, HDAC inhibitors have been found to induce multidrug resistance (MDR), which is an obstacle for the success of chemotherapy. The most common cause of MDR is considered to be the increased expression of adenosine triphosphate binding cassette (ABC) transporters. Numerous studies have identified that the upregulation of ABC transporters is often observed following treatment with HDAC inhibitors, particularly the increased expression of P-glycoprotein, which leads to drug efflux, reduces intracellular drug concentration and induces MDR. The present review summarizes the key ABC transporters involved in MDR following various HDAC inhibitor treatments in a range of cancer cell lines and also explored the potential mechanisms that result in MDR, including the effect of nuclear receptors, which are the upstream regulatory factors of ABC transporters.
组蛋白去乙酰化酶（HDAC）抑制剂正成为一类新型且有前景的抗肿瘤药物，已在临床上用于癌症治疗。两种HDAC抑制剂，伏立诺他和罗米地辛，已被美国食品药品监督管理局批准用于治疗T细胞淋巴瘤。然而，与常见的抗癌药物类似，HDAC抑制剂已被发现会诱导多药耐药（MDR），这是化疗成功的一个障碍。MDR最常见的原因被认为是三磷酸腺苷结合盒（ABC）转运蛋白的表达增加。大量研究已证实，在用HDAC抑制剂治疗后，经常会观察到ABC转运蛋白的上调，尤其是P-糖蛋白表达的增加，这会导致药物外排、降低细胞内药物浓度并诱导MDR。本综述总结了在一系列癌细胞系中，各种HDAC抑制剂治疗后参与MDR的关键ABC转运蛋白，并探讨了导致MDR的潜在机制，包括作为ABC转运蛋白上游调节因子的核受体的作用。
