The Antitumor Activity of hAMSCs Secretome in HT-29 Colon Cancer Cells Through Downregulation of EGFR/c-Src/IRTKS Expression and p38/ERK1/2 Phosphorylation.

Abstract

Colon cancer is considered as one of the main causes of mortality worldwide. Identifying a novel and more effective platform with fewer side effects is still progress. In various cancer types, Epidermal growth factor receptor (EGFR) and c-Src (a key mediator in EGFR signaling pathway) are the key targets for cancer therapy. Moreover, insulin receptor tyrosine kinase substrate (IRTKS or BAI1-associated protein 2-like 1: BAIAP2L1) is a member of the subfamily of inverse BAR (I-BAR) domain proteins, which mediates cell morphology and movement through regulation of actin polymerization. In this study, we employed a co-culture system using Transwell six-well plates. After 72 h, hAMSCs-treated HT-29 cells, EGFR, c-Src, IRTKS, p38, and ERK1/2 expression were analyzed using quantitative real time PCR (qRT-PCR) and western blot methods. The significant reduction in tumor cell growth and motility through downregulation of EGFR/c-Src/IRTKS expression and p38/ERK1/2 phosphorylation in HT-29 cells was demonstrated based on 2D and 3D cell culture models. The induction of cellular apoptosis was also found. Our results support the idea that the hAMSCS secretome has therapeutic effects on cancer cells. However, further experiments will be required to identify the exact molecular mechanisms.