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Evaluation of chemotherapeutics in a three-dimensional breast cancer model

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Abstract

Purpose

Utilization of miniaturized three-dimensional (3D) cell culture-based assays enables investigation into the anticancer activity of drug candidates and further elucidation of the anticancer profile of standard-of-care chemotherapeutic agents against tumor cells. Drug discovery assays established using 3D cell culture, which better recapitulate the tumor microenvironment, may more accurately reflect the antitumor activity of compounds.

Methods

Several standard-of-care anticancer drugs, epirubicin, paclitaxel and vinorelbine, were evaluated against a panel of breast cancer cell lines grown in a 3D cell culture microenvironment in the presence of extracellular matrix. A comparison of this antitumor activity in 3D conditions was made with that observed in traditional two-dimensional (2D) monolayer conditions.

Results

Examination of the above mentioned drugs against breast tumor cells cultured in 3D conditions demonstrated significantly altered potency and efficacy in comparison with cells propagated in a 2D monolayer system. The differences observed were cell line-dependent and drug-specific; the triple-negative cell line MDA-MB-231 and the endocrine receptor-positive cell line MCF-7 consistently displayed resistance to therapeutics with distinct modes of action (i.e., topoisomerase II and microtubules) in 3D cell culture in comparison with ErbB2 receptor-positive BT-474 cells.

Conclusion

The data presented herein demonstrates the cellular viability and physical changes observed within the 3D spheroid following exposure to drug, which is not always reflected in 2D cell culture models.

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Acknowledgments

This work was supported by an Australian Postgraduate Award and a Cancer Therapeutics CRC top-up scholarship for Carrie J. Lovitt and an Australian Postgraduate Award and Discovery Biology top-up scholarship for Todd B. Shelper.

Conflict of interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Discovery Biology, Eskitis Institute for Drug Discovery, Griffith University, Building N27, Brisbane Innovation Park, Nathan, QLD, 4111, Australia

    Carrie J. Lovitt, Todd B. Shelper & Vicky M. Avery

Authors
  1. Carrie J. Lovitt
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  2. Todd B. Shelper
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  3. Vicky M. Avery
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Correspondence to Vicky M. Avery.

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Lovitt, C.J., Shelper, T.B. & Avery, V.M. Evaluation of chemotherapeutics in a three-dimensional breast cancer model. J Cancer Res Clin Oncol 141, 951–959 (2015). https://doi.org/10.1007/s00432-015-1950-1

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  • DOI: https://doi.org/10.1007/s00432-015-1950-1

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