Sun Ruipu, Ying Ying, Tang Zhimin, Liu Ting, Shi Fuli, Li Huixia, Guo Taichen, Huang Shibo, Lai Ren
Jiangxi Province Key Laboratory of Tumor Pathogens and Molecular Pathology and Department of Pathophysiology, Schools of Basic Medical Sciences, Nanchang University Medical College, Nanchang, China.
Nanchang Joint Program, Queen Mary University of London, London, United Kingdom.
Protein Pept Lett. 2020;27(1):17-29. doi: 10.2174/0929866526666190926154248.
Currently, chemotherapy is one of the mainstays of oncologic therapies. But the efficacy of chemotherapy is often limited by drug resistance and severe side effects. Consequently, it is becoming increasingly important to investigate the underlying mechanism and overcome the problem of anticancer chemotherapy resistance. The solute carrier organic anion transporter family member 1B3 (SLCO1B3), a functional transporter normally expressed in the liver, transports a variety of endogenous and exogenous compounds, including hormones and their conjugates as well as some anticancer drugs. The extrahepatic expression of SLCO1B3 has been detected in different cancer cell lines and cancer tissues. Recently, accumulating data indicates that the abnormal expression and function of SLCO1B3 are involved in resistance to anticancer drugs, such as taxanes, camptothecin and its analogs, SN-38, and Androgen Deprivation Therapy (ADT) in breast, prostate, lung, hepatic, and colorectal cancer, respectively. Thus, more investigations have been implemented to identify the potential SLCO1B3-related mechanisms of cancer drug resistance. In this review, we focus on the emerging roles of SLCO1B3 protein in the development of cancer chemotherapy resistance and briefly discuss the mechanisms of resistance. Elucidating the function of SLCO1B3 in chemoresistance may bring out novel therapeutic strategies for cancer treatment.
目前，化疗是肿瘤治疗的主要手段之一。但化疗的疗效常常受到耐药性和严重副作用的限制。因此，研究其潜在机制并克服抗癌化疗耐药性问题变得越来越重要。溶质载体有机阴离子转运体家族成员1B3（SLCO1B3）是一种通常在肝脏中表达的功能性转运体，可转运多种内源性和外源性化合物，包括激素及其共轭物以及一些抗癌药物。已在不同癌细胞系和癌组织中检测到SLCO1B3的肝外表达。最近，越来越多的数据表明，SLCO1B3的异常表达和功能分别与乳腺癌、前列腺癌、肺癌、肝癌和结直肠癌对紫杉烷类、喜树碱及其类似物、SN-38以及雄激素剥夺疗法（ADT）等抗癌药物的耐药性有关。因此，人们开展了更多研究以确定与SLCO1B3相关的癌症耐药潜在机制。在本综述中，我们重点关注SLCO1B3蛋白在癌症化疗耐药性发展中的新作用，并简要讨论耐药机制。阐明SLCO1B3在化疗耐药中的功能可能会带来癌症治疗的新策略。
