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.

BACKGROUND: 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 (p15(INK4B) and p21(CIP1)) using a hanging drop 3D cell culture model. METHODS: 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. RESULTS: The study revealed a decrease in the TGF-βR/SMADs/c-MYC signaling pathway and an increase in levels of p15(INK4B), p21(CIP1), TNF-α, and IL-4/6/8. Additionally, a decrease in invasion was detected in HT-29 cells treated with hAMSCs. CONCLUSIONS: Our results could be useful in developing a new approach to treating cancer using hAMSCs' secretome.