The dual inhibitory effect of adipose-derived mesenchymal stem cell secretome on JAK2/STAT3 and PI3k/AKT/mTOR signaling pathways

Stem cells are considered as promising candidates to effectively hinder the proliferation of different types of cancers including hepatocellular carcinoma, Kaposi's sarcoma, as well as gastric and breast cancers.Mesenchymal stem cells (MSCs) have attracted a lot of attention among the different categories of such cells.Adipose tissue offers unique advantages as a source of MSCs.Based on some studies, the released substances from MSCs which are regarded as secretome can modulate the growth and survival of tumor cells, along with immunity and angiogenesis by affecting different signaling pathways.JAK/STAT and PI3k/AKT/mTOR signaling pathways play the main role in regulating growth, proliferation, apoptosis, and cancer metastasis.This study aims to assess the cytotoxic effect of human adipose-derived MSC (adMSC) secretome on two cancerous cell lines by co-culturing each cancerous cell line with adMSCs and performing MTT assay, as well as evaluating simultaneous inhibitory effect of adMSC secretome on the expression rates of the genes related to JAK2/STAT3 and PI3k/AKT/mTOR signaling pathways by conducting real-time PCR after co-culturing.The results indicated that adMSC secretome did not exert cytotoxic effect against epidermoid carcinoma (A431) cell line, leading to increased cell viability.However, the percentage of viable cancerous cells significantly reduced following co-culturing of gastric adenocarcinoma (AGS) cell line with adMSCs, indicating different cytotoxic potency of adMSC secretome towards these cell lines.adMSC secretome downregulated the expression rates of Jak2, STAT3, PI3k, and mTOR genes in both cocultured cell lines, despite different effects against A431 and AGS cell lines, indicating the significance of such signaling pathways in the growth and proliferation of each cancerous cell lines.The results provide opportunities for examining in vitro and in vivo cytotoxic potency of adMSC secretome against other types of cancers and further evaluation of its downstream mechanisms of action through cancer signaling pathways.Thus, they may lead to the use of adMSC secretome as a novel therapeutic agent in different types of cancers.