Open Access

Antitumor effects of cadmium against diethylnitrosamine‑induced liver tumors in mice

  • Authors:
    • Yu Nie
    • Bo Huang
    • An-Ling Hu
    • Yun-Yan Xu
    • Yan Zou
    • Yun Liu
    • Jie Liu
  • View Affiliations

  • Published online on: November 26, 2021     https://doi.org/10.3892/ol.2021.13151
  • Article Number: 33
  • Copyright: © Nie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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January-2022
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Copy and paste a formatted citation
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Spandidos Publications style
Nie Y, Huang B, Hu A, Xu Y, Zou Y, Liu Y and Liu J: Antitumor effects of cadmium against diethylnitrosamine‑induced liver tumors in mice. Oncol Lett 23: 33, 2022
APA
Nie, Y., Huang, B., Hu, A., Xu, Y., Zou, Y., Liu, Y., & Liu, J. (2022). Antitumor effects of cadmium against diethylnitrosamine‑induced liver tumors in mice. Oncology Letters, 23, 33. https://doi.org/10.3892/ol.2021.13151
MLA
Nie, Y., Huang, B., Hu, A., Xu, Y., Zou, Y., Liu, Y., Liu, J."Antitumor effects of cadmium against diethylnitrosamine‑induced liver tumors in mice". Oncology Letters 23.1 (2022): 33.
Chicago
Nie, Y., Huang, B., Hu, A., Xu, Y., Zou, Y., Liu, Y., Liu, J."Antitumor effects of cadmium against diethylnitrosamine‑induced liver tumors in mice". Oncology Letters 23, no. 1 (2022): 33. https://doi.org/10.3892/ol.2021.13151