Effect of suberoylanilide hydroxamic acid (SAHA) on breast cancer cells within a tumor-stroma microfluidic model

N Peela1, E S Barrientos, D Truong

  • 1School of Biological and Health Systems Engineering (SBHSE), Arizona State University, Tempe, Arizona 85287, USA. mnikkhah@asu.edu.

Insights

A novel 3D microfluidic platform precisely controls the tumor microenvironment for advanced cancer drug screening. This system demonstrated that suberoylanilide hydroxamic acid (SAHA) inhibits breast cancer cell migration and proliferation.

Area of Science:

  • Oncology
  • Biotechnology
  • Microfluidics

Background:

  • Metastatic cancer causes significant global mortality, highlighting the need for effective therapies.
  • Current in vitro models lack physiological relevance and precise control over the tumor microenvironment, limiting drug screening efficacy.
  • Existing 2D and 3D hydrogel platforms struggle with controlled cell distribution and matrix architecture.

Purpose of the Study:

  • To develop and validate a 3D microfluidic invasion platform for physiologically relevant anti-cancer drug studies.
  • To enable precise control over microenvironmental cues, including matrix composition, soluble factors, and cellular organization.
  • To assess the efficacy of anti-cancer drugs within a controlled tumor microenvironment.

Main Methods:

  • Development of a 3D microfluidic platform with compartmentalization for tumor and stromal fibroblasts.
  • Implementation of defined architecture to mimic tumor microenvironment and enable controlled drug transport.
  • Analysis of suberoylanilide hydroxamic acid (SAHA) effects on SUM159 breast cancer cells.

Main Results:

  • The 3D microfluidic platform successfully compartmentalized tumor and stromal cells in a defined architecture.
  • Pharmacokinetic drug transport to dense tumor regions was enabled by the platform design.
  • SAHA treatment significantly inhibited SUM159 breast cancer cell migration and proliferation.
  • SAHA was observed to decrease microtubule polarization in breast cancer cells.

Conclusions:

  • The developed 3D microfluidic platform offers precise control over the tumor microenvironment for anti-cancer drug evaluation.
  • This platform provides a more physiologically relevant model compared to conventional 2D or hydrogel-based systems.
  • SAHA demonstrates inhibitory effects on breast cancer cell behavior, warranting further investigation in controlled microenvironments.

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