Nedaplatin is a derivative of cisplatin and a DNA damage agent that can induce nephrotoxicity [1]. Nedaplatin enters cells through various transport proteins to bind to DNA, causing DNA distortion and damaging the DNA structure, and stimulates the production of reactive oxygen species, thereby inducing cellular oxidative stress[2]. Nedaplatin has been widely used to kill the proliferation of various tumor cells and has been employed to develop combined therapies to effectively inhibit tumor growth[3].
In vitro, Nedaplatin treatment for 48 hours significantly promoted cell death in HNE1 and CNE2 cells, with IC50 values of 2.75μg/ml and 1.49μg/ml, respectively[4]. Treatment with 10μg/ml Nedaplatin for 48 hours significantly induced apoptosis in SKOV3 cells, caused cell cycle arrest, accompanied by an increase in the expression of Bax, caspase-3 and caspase-9, and a decrease in the expression of Bcl-2 and MMP-2[5]. Treatment with 20μM Nedaplatin combined with 5μM ABT-737 for 48 hours led to depolarization of the mitochondrial membrane in A549 cells, promoting the degradation of Mcl-1 protein and the release of cytochrome c[6].
In vivo, Nedaplatin treatment via a single intravenous injection at a dose of 15mg/kg significantly induced the death of 15-week-old male rats within 10 days, and caused weight loss and kidney damage in the rats[7]. A single intravenous injection of 20mg/kg dose of Nedaplatin significantly induced tumor growth in a xenograft mouse model of Ma44 cells within 12 days [8].
References:
[1] Shimada M, Itamochi H, Kigawa J. Nedaplatin: a cisplatin derivative in cancer chemotherapy[J]. Cancer management and research, 2013: 67-76.
[2] Szupryczyński K, Szefler B. Interactions of Nedaplatin with Nucleobases and Purine Alkaloids: Their Role in Cancer Therapy[J]. Biomedicines, 2025, 13(7): 1551.
[3] Su X Y, Yin H T, Li S Y, et al. Intervention effects of nedaplatin and cisplatin on proliferation and apoptosis of human tumour cells in vitro[J]. Asian Pacific Journal of Cancer Prevention, 2012, 13(9): 4531-4536.
[4] Liu Z, Liu J, Li L, et al. Inhibition of autophagy potentiated the antitumor effect of nedaplatin in cisplatin-resistant nasopharyngeal carcinoma cells[J]. PloS one, 2015, 10(8): e0135236.
[5] Li W, Hanfeng L, Zhengwen C, et al. Nedaplatin Induced Apoptosis in Human Ovarian Cancer Cisplatin-resistant Cell Lines in vitro and Investigated Its Mechanism[J]. Cancer Research on Prevention and Treatment, 2012, 39(10): 1216-1220.
[6] Zhang C, Li Y L, Weng X, et al. Nedaplatin enhanced apoptotic effects of ABT-737 in human cancer cells via Mcl-1 inhibition[J]. Oncology Letters, 2016, 12(5): 4195-4202.
[7] Uehara T, Watanabe H, Itoh F, et al. Nephrotoxicity of a novel antineoplastic platinum complex, nedaplatin: a comparative study with cisplatin in rats[J]. Archives of toxicology, 2005, 79(8): 451-460.
[8] Matsumoto M, Takeda Y, Maki H, et al. Preclinical in vivo antitumor efficacy of nedaplatin with gemcitabine against human lung cancer[J]. Japanese Journal of Cancer Research: Gann, 2001, 92(1): 51.
Nedaplatin是顺铂的衍生物，是一种DNA损伤剂，可诱导肾毒性[1]。Nedaplatin可通过多种转运蛋白进入细胞，然后与DNA结合，导致DNA扭曲并破坏DNA结构，同时刺激活性氧的产生，从而诱导细胞氧化应激[2]。Nedaplatin已被广泛用于杀伤多种肿瘤细胞的增殖，并已被用于开发联合疗法以有效抑制肿瘤生长[3]。
在体外，Nedaplatin处理48小时显著促进了HNE1和CNE2细胞的死亡，IC50值分别为2.75μg/ml和1.49μg/ml [4]。使用10μg/ml的Nedaplatin处理SKOV3细胞48小时，显著诱导了细胞凋亡，引起了细胞周期阻滞，同时伴随Bax、caspase-3和caspase-9表达升高，以及Bcl-2和MMP-2表达降低[5]。使用20μM的Nedaplatin联合5μM的ABT-737处理A549细胞48小时，导致线粒体膜去极化，促进了Mcl-1蛋白降解和细胞色素c释放[6]。
在体内，单次静脉注射15mg/kg剂量的Nedaplatin，在10天内显著诱导了15周龄雄性大鼠的死亡，并导致大鼠体重下降和肾脏损伤[7]。单次静脉注射20mg/kg剂量的Nedaplatin，在12天内显著促进了Ma44细胞异种移植小鼠模型中的肿瘤生长[8]。