Huang Yaxin, Sun Guohui, Sun Xiaodong, Li Feifan, Zhao Lijiao, Zhong Rugang, Peng Yongzhen
Beijing Key Laboratory of Environment and Viral Oncology, College of Life Science and Chemistry, Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China.
National Engineering Laboratory for Advanced Municipal Wastewater Treatment & Reuse Technology, Engineering Research Center of Beijing, Beijing University of Technology, Beijing 100124, China.
Cancers (Basel). 2020 Nov 11;12(11):3332. doi: 10.3390/cancers12113332.
Lonidamine (LND) has the ability to resist spermatogenesis and was first used as an anti-spermatogenic agent. Later, it was found that LND has a degree of anticancer activity. Currently, LND is known to target energy metabolism, mainly involving the inhibition of monocarboxylate transporter (MCT), mitochondrial pyruvate carrier (MPC), respiratory chain complex I/II, mitochondrial permeability transition (PT) pore, and hexokinase II (HK-II). However, phase II clinical studies showed that LND alone had a weak therapeutic effect, and the effect was short and reversible. Interestingly, LND does not have the common side effects of traditional chemotherapeutic drugs, such as alopecia and myelosuppression. In addition, LND has selective activity toward various tumors, and its toxic and side effects do not overlap when combined with other chemotherapeutic drugs. Therefore, LND is commonly used as a chemosensitizer to enhance the antitumor effects of chemotherapeutic drugs based on its disruption of energy metabolism relating to chemo- or radioresistance. In this review, we summarized the combination treatments of LND with several typical chemotherapeutic drugs and several common physical therapies, such as radiotherapy (RT), hyperthermia (HT), and photodynamic therapy (PDT), and discussed the underlying mechanisms of action. Meanwhile, the development of novel formulations of LND in recent years and the research progress of LND derivative adjudin (ADD) as an anticancer drug were also discussed.
氯尼达明（LND）具有抑制精子发生的能力，最初被用作抗精子生成剂。后来，人们发现LND具有一定程度的抗癌活性。目前已知LND靶向能量代谢，主要涉及抑制单羧酸转运体（MCT）、线粒体丙酮酸载体（MPC）、呼吸链复合体I/II、线粒体通透性转换（PT）孔和己糖激酶II（HK-II）。然而，II期临床研究表明，单独使用LND治疗效果较弱，且效果短暂且可逆。有趣的是，LND没有传统化疗药物常见的副作用，如脱发和骨髓抑制。此外，LND对各种肿瘤具有选择性活性，与其他化疗药物联合使用时其毒副作用不重叠。因此，基于其对与化疗或放疗抗性相关的能量代谢的破坏，LND通常用作化学增敏剂以增强化疗药物的抗肿瘤作用。在本综述中，我们总结了LND与几种典型化疗药物以及几种常见物理疗法（如放射疗法（RT）、热疗（HT）和光动力疗法（PDT））的联合治疗，并讨论了其潜在的作用机制。同时，还讨论了近年来LND新型制剂的开发以及LND衍生物阿地君定（ADD）作为抗癌药物的研究进展。
