Antitumor efficacy of EDTA co-treatment with cisplatin in tumor-bearing mice

Ethylenediamine tetraacetic acid (EDTA) is used in various medical applications. The aim of this study is to investigate the antitumor efficacy of EDTA alone or with cisplatin (Cis). Fifty male albino mice were used to assess the median lethal dose (LD50) of EDTA via intraperitoneal (i.p) injection. To determine the antitumor activity, fifty female albino mice were divided into five groups as the following; Group 1 (Gp1) was negative control; (Gp2-5) inoculated i.p with 2×106 Ehrlich Ascites Carcinoma (EAC) cells/mouse. After one day, Gp3, Gp4 and Gp5 injected with Cis (2 mg/kg), EDTA (25 mg/kg) and Cis (2 mg/kg)/EDTA (25 mg/kg) for six days, respectively. At day 14, all groups were sacrificed to assess the tumor profile, liver enzymes (alanine transaminases and aspartate transaminases), kidney function (urea and creatinine) and electrolytes (Na+, K+ and Ca2+). The results showed that the i.p LD50 of EDTA was 250 mg/kg. Treatment with EDTA alone did not show any antitumor activity and did not interfere with the antitumor efficacy of Cis. Biochemical findings revealed that EDTA had mild toxicity on liver and kidneys functions. In summary, EDTA had no antitumor effect and did not alter the Cis efficacy.

乙二胺四乙酸（Ethylenediamine tetraacetic acid, EDTA）在诸多医学领域中均有应用。本研究旨在探究乙二胺四乙酸单药或与顺铂（cisplatin, Cis）联用的抗肿瘤活性。研究选取50只雄性白化小鼠，通过腹腔内（intraperitoneal, i.p.）注射途径测定乙二胺四乙酸的半数致死量（median lethal dose, LD50）。为评估抗肿瘤活性，另选取50只雌性白化小鼠分为5组，具体分组如下：第1组（Gp1）为阴性对照组；第2至5组（Gp2~Gp5）小鼠均经腹腔接种2×10^6个艾氏腹水癌（Ehrlich Ascites Carcinoma, EAC）细胞。接种1天后，分别对Gp3、Gp4、Gp5组小鼠连续6天给药：Gp3给予顺铂（2 mg/kg），Gp4给予乙二胺四乙酸（25 mg/kg），Gp5给予顺铂（2 mg/kg）与乙二胺四乙酸（25 mg/kg）联用方案。于第14天时处死所有小鼠，检测肿瘤相关指标、肝功能指标（丙氨酸转氨酶与天冬氨酸转氨酶）、肾功能指标（尿素与肌酐）以及电解质（Na+、K+与Ca2+）水平。结果显示，乙二胺四乙酸的腹腔注射半数致死量为250 mg/kg。单用乙二胺四乙酸未表现出抗肿瘤活性，亦未影响顺铂的抗肿瘤效果。生化检测结果显示，乙二胺四乙酸对肝肾功能存在轻度毒性。综上，乙二胺四乙酸无抗肿瘤作用，亦未改变顺铂的抗肿瘤疗效。