• Assessing the effect of HCT116-released exosomes on mRNA expression level of ATF4, ATF and DDIT3 in peripheral blood mononuclear cells ( PBMC ) isolated form healthy individuals
  • Amirhossein Shafieian,1,*
    1. Tehran university of medical science


  • Introduction: Today, colon cancer is the third most common cancer in the world. According to epidemiologic studies, this cancer is the second and third most common cancer in men and women, respectively. In 2022, cases of incidence and mortality due to this disease is about 1.9 million and 900 thousand people, respectively. One of the mechanisms of immune response regulation by tumor cells is the secretion of extracellular vesicles (EV). Tumor-derived extracellular vesicles (TEX) play a key role in reprogramming the immune system by delivering their cargo to various immune cells. Several studies have shown that tumor-derived exosomes (TEX) play an important role in angiogenesis, tumor growth, Invasion, metastasis, escape from the immune system response through increasing the expression of immune checkpoints and induction of apoptosis in activated CD8+ T cells, suppression of natural killer cells (NK cells), interference in monocyte differentiation and proliferation of Treg and MDSC cells. The things mentioned in relation to the effect of exosomes on the immune system are consistent with the effect exerted by ER Stress. The purpose of this study was to investigate the expression changes of some genes involved in the UPR pathway in peripheral blood mononuclear cells. It is the peripheral blood of healthy people which has been treated with tumor exosomes.
  • Methods: In this study, HCT-116 cells, which are colorectal cancer cells, were cultured, then tumor exosomes were purified and confirmatory tests were performed to check the presence of exosomes. Then, these exosomes were treated with half of the IC50 concentration obtained from the MTT test on PBMC cells isolated from 6 healthy individuals, and finally, assessing the level of expression of ATF4, ATF6 and DDIT3 genes using qRT-PCR .
  • Results: In this study, the effect of exosomes of colorectal cancer cell line (HCT-116) was investigated on the expression of ATF4, ATF6 and DDIT3 genes. The expression levels of none of the ATF4, ATF6 and DDIT3 genes were significantly different between the groups treated with exosomes isolated from HCT-116 and exosomes isolated from the complete medium containing 5% FBS and the group treated with PBS (P>0.05)
  • Conclusion: In general, this study, showed that there is not a significant difference in the expression of ATF4, ATF6 and DDIT3 genes in the PBMC cells of healthy individuals which treated with exosomes extracted from the supernatant of the HCT-116 cell line culture medium compared to the Control groups (group treated with exosomes isolated from complete medium containing 5% FBS and group treated with PBS).
  • Keywords: HCT116, UPR, PBMC, ATF4, ATF6, DDIT3