# Investigating the Impact of the Secretome From hAMSCs on HT‐29 Colon Cancer Cells via TNF‐α/TGF‐β/c‐MYC Signaling Pathways Using a Three‐Dimensional Cell Culture Model

## TL;DR

This study explores how the secretome of hAMSCs affects colon cancer cells through specific signaling pathways, suggesting a new approach for cancer treatment.

## Contribution

The novel contribution is the investigation of hAMSCs secretome's impact on HT-29 cells using a 3D model and specific signaling pathways.

## Key findings

- The TGF-βR/SMADs/c-MYC signaling pathway was reduced in HT-29 cells treated with hAMSCs secretome.
- Levels of p15INK4B, p21CIP1, TNF-α, and IL-4/6/8 increased following treatment.
- Cell invasion decreased in HT-29 cells exposed to hAMSCs secretome.

## Abstract

Colon cancer is recognized as one of the predominant reasons of death globally. The ongoing cancer treatment techniques have not been successful; so, a strong and unique platform is needed. Interestingly, it has been discovered that stem cells offer a valuable and promising platform in cancer treatment. The goal of this study is to explore the influences of hAMSCs secretome on HT‐29 colon cancer cells by analyzing TNF‐α/TGF‐βR/c‐MYC signaling pathway, expression of interleukins (IL)‐4/6/8, and cyclin‐dependent kinase (CDK) inhibitory proteins (p15INK4B and p21CIP1) using a hanging drop 3D cell culture model.

In this study, a coculture system was employed. After 3 days, hAMSCs' secretome was collected and its effects on tumor formation, inflammation, and cell invasion were analyzed using Western blot, scratch assay, qPCR, and ELISA.

The study revealed a decrease in the TGF‐βR/SMADs/c‐MYC signaling pathway and an increase in levels of p15INK4B, p21CIP1, TNF‐α, and IL‐4/6/8. Additionally, a decrease in invasion was detected in HT‐29 cells treated with hAMSCs.

Our results could be useful in developing a new approach to treating cancer using hAMSCs' secretome.