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Background <p>Breast cancer is one of the most common cancers among women worldwide, and metastasis plays an important role in its lethality. Silymarin (SLY) is a natural compound that has exhibited potential anticancer effects. However, its effects on the metastatic properties of different breast cancer cell lines remain unknown. Therefore, this study aimed to investigate the effects of SLY on the metastatic properties of two breast cancer cell lines (MCF-7 and MDA-MB-231) and evaluate differences between two-dimensional (2D) and three-dimensional (3D) cell culture models.</p> Methods <p>This study used 2D and 3D cell culture systems to evaluate the effects of SLY on cell proliferation, migration, and epithelial–mesenchymal transition (EMT). The effective dose of SLY was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell viability assays in 2D and 3D cultures. In 2D cultures, wound healing assays, polymerase chain reaction (PCR) to evaluate mRNA levels and immunohistochemical analyses to evaluate protein expression. In 3D cultures, spheroids were formed, and Transwell migration assays, PCR for mRNA levels, and immunohistochemical analyses for protein expression were conducted.</p> Results <p>SLY effectively modulated proliferation, migration, and EMT in both cell lines. Notably, the 3D microenvironment exerted differential effects on drug sensitivity: MCF-7 cells showed increased sensitivity to SLY in 3D culture, whereas MDA-MB-231 cells exhibited increased resistance compared to 2D models.</p> Conclusions <p>These findings suggest that SLY exhibits promising antimetastatic potential in vitro, warranting further in vivo and clinical investigations to evaluate its efficacy as a supportive therapeutic candidate for breast cancer treatment. This study emphasizes the importance of 3D culture models for accurately evaluating the efficacy of anticancer drugs. Notably, SLY's effect on MMP-9 expression was found to be environment-dependent, showing a significant reduction specifically in the 3D spheroid model, which highlights its potential antimetastatic efficacy in more biomimetic settings.</p>

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Comparative evaluation of the effects of Silymarin on the metastatic characteristics of MCF-7 and MDA-MB-231 breast cancer cells with two-dimensional and three-dimensional culture methods

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月11日

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  • Tuğçe Aladağ,
  • Fatma Firat,
  • Hülya Çetin,
  • Evrim Suna Arikan Söylemez

摘要

Background

Breast cancer is one of the most common cancers among women worldwide, and metastasis plays an important role in its lethality. Silymarin (SLY) is a natural compound that has exhibited potential anticancer effects. However, its effects on the metastatic properties of different breast cancer cell lines remain unknown. Therefore, this study aimed to investigate the effects of SLY on the metastatic properties of two breast cancer cell lines (MCF-7 and MDA-MB-231) and evaluate differences between two-dimensional (2D) and three-dimensional (3D) cell culture models.

Methods

This study used 2D and 3D cell culture systems to evaluate the effects of SLY on cell proliferation, migration, and epithelial–mesenchymal transition (EMT). The effective dose of SLY was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell viability assays in 2D and 3D cultures. In 2D cultures, wound healing assays, polymerase chain reaction (PCR) to evaluate mRNA levels and immunohistochemical analyses to evaluate protein expression. In 3D cultures, spheroids were formed, and Transwell migration assays, PCR for mRNA levels, and immunohistochemical analyses for protein expression were conducted.

Results

SLY effectively modulated proliferation, migration, and EMT in both cell lines. Notably, the 3D microenvironment exerted differential effects on drug sensitivity: MCF-7 cells showed increased sensitivity to SLY in 3D culture, whereas MDA-MB-231 cells exhibited increased resistance compared to 2D models.

Conclusions

These findings suggest that SLY exhibits promising antimetastatic potential in vitro, warranting further in vivo and clinical investigations to evaluate its efficacy as a supportive therapeutic candidate for breast cancer treatment. This study emphasizes the importance of 3D culture models for accurately evaluating the efficacy of anticancer drugs. Notably, SLY's effect on MMP-9 expression was found to be environment-dependent, showing a significant reduction specifically in the 3D spheroid model, which highlights its potential antimetastatic efficacy in more biomimetic settings.