JQ1 Suppresses The Effect Of Mesenchymal Stem Cells Conditioned Medium Promoting Gastric Cancer Cell

Objective:Previous studies reported that human bone marrow mesenchymal stem cells(h BM-MSCs) were related to tumor progression. C-Myc, as a well-known proto-oncogene, has an important role in gastric carcinogenesis. JQ1 as c-Myc inhibitor has shown anti-proliferative effects in many cancers. The aim of the present study was to examine whether JQ1 can inhibit the side effect of tumor induced by h BM-MSCs-CM.Methods: The mononuclear cell of human bone marrow was isolated by Ficoll separation liquid and uesd adherent separation to cluture h BM-MSCs. The morphological of h BM-MSCs were observed by phase contrast microscope, and the surface markers of h BM-MSCs was analysed by flow cytometry; The culture medium of h BM-MSCs(h BM-MSCs-CM) was collected; The gastric cancer cells(MGC-803 cells) were treated with H-DMEM, DMSO, h BM-MSCs-CM, JQ1 and JQ1+ h BM-MSCs-CM for 48 h, which were used to analysis the effect of JQ1 on the proliferation, migration assay, cell cycle and the expression of c-Myc and stemness markers(Sall4, Nanog, Oct4)of MGC-803 cells. At the same time, to observe the growth status of tumor, the thirty BALB/c-nu/nu male mice(aged 4-5 weeks) were used to constract xenograft tumor model. Proliferation ability was detected by MTT assay and colony formation assay. Scratct-wound assay and transwell migration assay was used to observe migration assay. Flow cytometry was used to analysis the changes of cell cycle. The expression of c-Myc、stemness markers(Sall4, Nanog, Oct4)、Bcl-2 and Bax were detected by western blot.Results : Human bone marrow mesenchymal stem cells(h BM-MSCs) were successfully isolated and identified. In vitro, we found that JQ1 decreased the expression of c-Myc and stemness markers in h BM-MSCs-CM treated tumor cells group. Moreover, JQ1 dispalyed an anti-proliferative effect in vitro, but had little effect on cell cycle arrest and apoptosis. Additionly, h BM-MSCs-CM favored gastric cancer cells metastasis apparently, while JQ1 suppressed h BM-MSCs-CM induced metastasis of MGC-803 cells. Consistent with the results in vitro, JQ1 suppresses h BM-MSCs-CM induced the pro-proliferative effect apparently and decreased the expression of stemness markers in vivo.Conclusion: JQ1 can suppressed the effect of h BM-MSCs-CM on gastric cancer, making it possible to prevent the h BM-MSCs from promoting tumor growth in clinic.