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Introduction <p>Cervical cancer is the fourth most common malignancy in females worldwide. Silymarin, a flavonoid with established anti-inflammatory properties, shows promise in oncology. Conditioned medium (CM) of Mesenchymal stem cell (MSC) exerts paracrine immunomodulatory effects. This study evaluated the combined impact of CM of adipose tissue-derived MSC (AD-MSC) and nanosilymarin on peripheral blood mononuclear cells (PBMC) from healthy donors co-cultured with HeLa cervical cancer cells.</p> Methods <p>AD-MSCs were isolated from adipose tissue via collagenase I digestion, characterized by immunophenotyping and multilineage differentiation potential. Apoptosis (Annexin V/PI), proliferation (MTT assay), and gene expression of IFN-γ, TNF-α, IL-4, and TGF-β (qRT-PCR) were assessed in PBMC treated with AD-MSC-CM (50%) and/or nanosilymarin (25 µM) for 48&#xa0;h, in monoculture or HeLa co-culture.</p> Results <p>In PBMC-HeLa co-culture, nanosilymarin (different concentrations) with 50% MSC-CM significantly reduced PBMC proliferation. Nanosilymarin (25 µM) plus MSC-CM induced marked HeLa apoptosis. Both agents together upregulated IFN-γ expression in PBMC, in monoculture and co-culture, without altering TNF-α, IL-4, or TGF-β.</p> Conclusion <p>Nanosilymarin combined with AD-MSC-CM enhances PBMC-mediated anti-tumor immunity via IFN-γ upregulation and promotes HeLa apoptosis, suggesting synergistic potential for cervical cancer immunotherapy. Mechanistic studies and dose optimization are warranted.</p>

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Effects of nanosilymarin and conditioned medium of adipose-derived mesenchymal stem cells on peripheral blood mononuclear cells co-cultured with HeLa cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月16日

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  • Nafiseh Daneshi,
  • Mahmoud Mahmoudi,
  • Seyed Abdolrahim Rezaee,
  • Majid Khoshmirsafa,
  • Niayesh Salar,
  • Solmaz Kheradmand,
  • Fahimeh Lavi Arab,
  • Fatemeh Faraji

摘要

Introduction

Cervical cancer is the fourth most common malignancy in females worldwide. Silymarin, a flavonoid with established anti-inflammatory properties, shows promise in oncology. Conditioned medium (CM) of Mesenchymal stem cell (MSC) exerts paracrine immunomodulatory effects. This study evaluated the combined impact of CM of adipose tissue-derived MSC (AD-MSC) and nanosilymarin on peripheral blood mononuclear cells (PBMC) from healthy donors co-cultured with HeLa cervical cancer cells.

Methods

AD-MSCs were isolated from adipose tissue via collagenase I digestion, characterized by immunophenotyping and multilineage differentiation potential. Apoptosis (Annexin V/PI), proliferation (MTT assay), and gene expression of IFN-γ, TNF-α, IL-4, and TGF-β (qRT-PCR) were assessed in PBMC treated with AD-MSC-CM (50%) and/or nanosilymarin (25 µM) for 48 h, in monoculture or HeLa co-culture.

Results

In PBMC-HeLa co-culture, nanosilymarin (different concentrations) with 50% MSC-CM significantly reduced PBMC proliferation. Nanosilymarin (25 µM) plus MSC-CM induced marked HeLa apoptosis. Both agents together upregulated IFN-γ expression in PBMC, in monoculture and co-culture, without altering TNF-α, IL-4, or TGF-β.

Conclusion

Nanosilymarin combined with AD-MSC-CM enhances PBMC-mediated anti-tumor immunity via IFN-γ upregulation and promotes HeLa apoptosis, suggesting synergistic potential for cervical cancer immunotherapy. Mechanistic studies and dose optimization are warranted.