The Microwell-mesh: A high-throughput 3D prostate cancer spheroid and drug-testing platform

Sci Rep. 2018 Jan 10;8(1):253. doi: 10.1038/s41598-017-18050-1.

Abstract

Treatment following early diagnosis of Prostate cancer (PCa) is increasingly successful, whilst the treatment of advanced and metastatic PCa remains challenging. A major limitation in the development of new therapies is the prediction of drug efficacy using in vitro models. Classic in vitro 2-dimensional (2D) cell monolayer cultures are hypersensitive to anti-cancer drugs. As a result, there has been a surge in the development of platforms that enable three dimensional (3D) cultures thought to better replicate natural physiology and better predict drug efficacy. A deficiency associated with most 3D culture systems is that their complexity reduces the number of replicates and combination therapies that can be feasibly evaluated. Herein, we describe the use of a microwell platform that utilises a nylon mesh to retain 3D micro-tumours in discrete microwells; termed the Microwell-mesh. The Microwell-mesh enables the manufacture of ~150 micro-tumours per well in a 48-well plate, and response to anti-tumour drugs can be readily quantified. Our results demonstrate that 3D micro-tumours, unlike 2D monolayers, are not hypersensitive to Docetaxel or Abiraterone Acetate, providing a superior platform for the evaluation of sequential drug treatment. In summary, the Microwell-mesh provides an efficient 3D micro-tumour platform for single and sequential drug screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Docetaxel
  • Drug Screening Assays, Antitumor / methods*
  • High-Throughput Screening Assays*
  • Humans
  • Male
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Spheroids, Cellular
  • Taxoids / pharmacology
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Taxoids
  • Docetaxel