Abstract: Objective To investigate the effect of exosomes derived from human gastric cancer cell line AGS and miR-106a on the phenotype of peritoneal mesothelial cells line HMrSV5. Methods Exosomes from AGS cells were isolated and incubated with HMrSV5 cells. Then exosome secretion inhibitor GW4869 was added. miR-106a expression was detected by qPCR, HMrSV5 cells proliferation and apoptosis were detected by EdU and flow cytometry technology. After the AGS cells were transfected with miR-106a mimic or inhibitor, the migration of HMrSV5 cells was detected by Transwell assay, and the expression of Smad7, TIMP2, MMP2, MMP9 and α-SMA was detected by Western blot. After treatment with TGF-β, the expression of Smad7, Smad2/3 and p-Smad2/3 was detected by Western blot. Results The exosomes of AGS cells highly expressed miR-106a (P＜0.01), and incubation with HMrSV5 cells significantly inhibited its proliferation and promoted the early apoptosis rate(P＜0.05). After transfection of miR-106a mimic, the exosomes from AGS cells promoted the migration of HMrSV5 cells (P＜0.001). Meanwhile, the expression of Smad7 and TIMP2 was decreased, but the expression of MMP2, MMP9 and α-SMA was increased. After treatment with TGF-β, the expression of Smad7 decreased but the expression of Smad2/3 and p-Smad2/3 increased. Conclusions Exosomes derived from human gastric cancer AGS cells can promote apoptosis, inhibit proliferation and enhance migration of human peritoneal mesothelial HMrSV5 cells, which may be related to the transport of miR-106a targeting Smad7 and TIMP2.

Key words: gastric cancer, mesothelial cells, exosomes, microRNA, Smad7