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Updated: Jul 23, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

Cytokeratin expression results in a drug-resistant phenotype to six different chemotherapeutic agents

J M Anderson1, L M Heindl, P A Bauman

  • 1Departments of Radiation Oncology, Pharmacology and Toxicology, Medicine, and Surgery, University of Arizona Cancer Center, Tucson, Arizona 85724, USA.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|January 1, 1996
PubMed

Insights

Introducing a cytokeratin network into cells confers resistance to several DNA-damaging drugs, suggesting a protective role against apoptosis. This cytokeratin-dependent drug resistance is cell-line specific and agent-dependent.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The function of the cytokeratin network, an abundant cytoplasmic system, remains largely unknown.
  • Previous research indicated that introducing a cytokeratin network into eukaryotic cells can lead to a drug resistance phenotype.

Purpose of the Study:

  • To investigate the universality of cytokeratin-mediated drug resistance.
  • To determine the survival response of different cell lines to various DNA-damaging agents.
  • To correlate in vitro survival assays with in vivo responses to DNA damage by examining apoptotic responses.

Main Methods:

  • Investigated the survival of two distinct cell lines using two assays for cell survival.
  • Exposed cells to six different DNA-damaging agents: mitoxantrone, doxorubicin, melphalan, bleomycin, mitomycin C, cisplatin, and UV irradiation.
  • Compared the apoptotic response of cytokeratin-positive and cytokeratin-negative cell lines.

Main Results:

  • Cytokeratin networks conferred resistance to mitoxantrone, doxorubicin, melphalan, bleomycin, and mitomycin C in cytokeratin-positive cell lines.
  • No survival advantage was observed with cisplatin or UV irradiation.
  • Cytokeratin-positive cell lines showed protection against apoptosis, whereas cytokeratin-negative cell lines underwent apoptosis when exposed to mitoxantrone.

Conclusions:

  • Cytokeratin-dependent drug resistance is observed across different cell lines but is not universal for all DNA-damaging agents.
  • The mechanism of this drug resistance may involve cytokeratin-conferred protection against apoptosis.

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