Metallothionein-mediated resistance to multiple drugs can be induced by several anticancer drugs in mice

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Updated: Oct 29, 2026

Anticancer Metal Complexes: Synthesis and Cytotoxicity Evaluation by the MTT Assay
11:14

Anticancer Metal Complexes: Synthesis and Cytotoxicity Evaluation by the MTT Assay

Published on: November 10, 2013

Y Okazaki1, N Miura, M Satoh

  • 1Department of Public Health and Molecular Toxicology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.

Biochemical and Biophysical Research Communications
|May 20, 1998
PubMed

Insights

Metallothionein (MT) in tumors can suppress chemotherapy effectiveness. Increased MT levels reduce the efficacy of certain anticancer drugs, potentially leading to multidrug resistance in patients.

Area of Science:

  • Biochemistry
  • Oncology
  • Pharmacology

Background:

  • Metallothionein (MT) is a protein involved in cellular defense mechanisms.
  • The role of MT in tumor chemosensitivity remains incompletely understood.
  • Understanding MT's impact is crucial for optimizing cancer treatment strategies.

Purpose of the Study:

  • To investigate the influence of metallothionein on the chemosensitivity of transplanted tumors in mice.
  • To determine which anticancer drugs are affected by elevated MT levels.
  • To explore the potential of MT induction by chemotherapy to cause multidrug resistance.

Main Methods:

  • Transplanted tumors in mice were utilized as a model system.
  • Tumor metallothionein (MT) concentrations were manipulated and measured.
  • The antitumor activities of various chemotherapeutic agents were assessed in vivo.
  • The effect of chemotherapy on MT levels within tumors was evaluated.

Main Results:

  • Elevated MT levels (twice the control) significantly suppressed the antitumor activity of cisplatin, adriamycin, bleomycin, peplomycin, cyclophosphamide, and melphalan.
  • Mitomycin C, 5-fluorouracil, and vinblastine showed minimal sensitivity to increased MT concentrations.
  • All tested antitumor drugs increased MT concentration in transplanted tumors to levels that inhibited their own efficacy.

Conclusions:

  • Metallothionein plays a significant role in mediating resistance to several key chemotherapeutic agents.
  • Chemotherapy-induced MT upregulation may contribute to the development of multidrug resistance in tumors.
  • Targeting MT or its induction pathways could be a strategy to enhance chemotherapy effectiveness.

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