Nie Yu, Huang Bo, Hu An-Ling, Xu Yun-Yan, Zou Yan, Liu Yun, Liu Jie
Key Lab for Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China.
School of Public Health, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China.
Oncol Lett. 2022 Jan;23(1):33. doi: 10.3892/ol.2021.13151. Epub 2021 Nov 26.
Cadmium (Cd) has been reported to exhibit antitumor effects against chemically induced liver tumors. However, the antitumor effects of Cd are not completely understood. Metallotherapy, the use of a toxic metal to attack liver tumors, could be a viable strategy. In the present study, 8-week old, male, C57BL/6 mice were administered injections of diethylnitrosamine (DEN) (90 mg/kg, and then 50 mg/kg 2 weeks later), followed by liver tumor promotion with carbon tetrachloride. Cadmium chloride was administered in the drinking water (1000 ppm) from 21-40 weeks after DEN initiation. Body weights were recorded and liver tumor formation was monitored via ultrasound. At the end of experiments, livers were removed, weighed, and the tumor incidence, tumor numbers and tumor size scores were recorded. Liver histology and metallothionein (MT) immunostaining were performed. After DEN injection, animal body weight decreased, and then slowly recovered with time. Cd treatment did not affect animal body weight gain. Ultrasound analysis detected liver tumors 35 weeks after DEN injection, and the mice were necropsied at 40 weeks. Liver/body weight ratios increased in the DEN and DEN + Cd groups. Cd treatment decreased the tumor incidence (71 vs. 17%), tumor numbers (15 vs. 2) and tumor scores (22 vs. 3) when compared with the DEN only group. Histopathology showed hepatocyte degeneration in all groups, and immunohistochemistry showed MT-deficiency in the liver tumors, while MT staining was intensified in the surrounding tissues. Reverse transcription-quantitative PCR showed increases in α-fetoprotein level in DEN-treated livers, and increases in MT-2 and tumor necrosis factor α (TNFα) levels in Cd-treated livers. Thus, it was concluded that Cd is effective in the suppression of DEN-induced liver tumors, and that the mechanisms may be related to MT-deficiency in tumors and the induction of TNFα to kill tumor cells.
据报道，镉（Cd）对化学诱导的肝肿瘤具有抗肿瘤作用。然而，镉的抗肿瘤作用尚未完全明确。金属疗法，即使用有毒金属攻击肝肿瘤，可能是一种可行的策略。在本研究中，对8周龄的雄性C57BL/6小鼠注射二乙基亚硝胺（DEN）（90mg/kg，2周后再注射50mg/kg），随后用四氯化碳促进肝肿瘤形成。从DEN注射后第21至40周，在饮水中给予氯化镉（1000ppm）。记录体重，并通过超声监测肝肿瘤形成。实验结束时，取出肝脏，称重，并记录肿瘤发生率、肿瘤数量和肿瘤大小评分。进行肝脏组织学检查和金属硫蛋白（MT）免疫染色。注射DEN后，动物体重下降，随后随时间缓慢恢复。镉处理不影响动物体重增加。超声分析在DEN注射后35周检测到肝肿瘤，并在40周时对小鼠进行尸检。DEN组和DEN + Cd组的肝/体重比增加。与仅DEN组相比，镉处理降低了肿瘤发生率（71%对17%）、肿瘤数量（15个对2个）和肿瘤评分（22分对3分）。组织病理学显示所有组均有肝细胞变性，免疫组织化学显示肝肿瘤中MT缺乏，而周围组织中MT染色增强。逆转录定量PCR显示，DEN处理的肝脏中α-甲胎蛋白水平升高，镉处理的肝脏中MT-2和肿瘤坏死因子α（TNFα）水平升高。因此，得出结论，镉对抑制DEN诱导的肝肿瘤有效，其机制可能与肿瘤中MT缺乏以及诱导TNFα杀伤肿瘤细胞有关。
