PMID- 37057281 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230415 IS - 1837-9664 (Print) IS - 1837-9664 (Electronic) IS - 1837-9664 (Linking) VI - 14 IP - 4 DP - 2023 TI - Inhibition of STAT3 signaling as critical molecular event in HUC-MSCs suppressed Glioblastoma Cells. PG - 611-627 LID - 10.7150/jca.77905 [doi] AB - Objective: We investigated the effect of human umbilical cord mesenchymal stem cells (HUC-MSCs) supernatants on proliferation, migration, invasion, and apoptosis in glioblastoma (GBM) cell lines RG-2, U251, U87-MG, and LN-428, as well as their apoptosis and autophagy-mediated through IL-6/JAK2/STAT3 signaling pathway to explore the molecular mechanisms. Methods: In this study, RG-2, U251, U87-MG, and LN-428 cells were treated with 9 mg/ml HUC-MSCs supernatants. Their responses to HUC-MSCs supernatants treatment and the status of STAT3 signaling were analyzed by multiple experimental approaches to elucidate the importance of HUC-MSCs supernatants for GBM. Results: The results demonstrated that after treatment with HUC-MSCs supernatants, in vitro proliferation of RG-2, U251, U87-MG, and LN-428 cells were inhibited, and their sustained growth was also blocked. RG-2, U251, and U87-MG cells showed significant S phase accumulation, while LN-428 cells were blocked in G0/G1 phase. Their migratory invasive capacities were inhibited, and their apoptosis and autophagy ratios were increased. These effects were mediated through the IL-6/JAK2/STAT3 and its downstream signaling pathway. Conclusion: Our data showed that HUC-MSCs supernatants had anti-tumor effects on GBM cells. It inhibited the proliferation, migration, and invasion of GBM cells and promoted their apoptosis. Negative regulation of the IL-6/JAK2/STAT3 signaling pathway enhanced apoptosis and autophagy in tumor cells, thereby improving the therapeutic effect on GBM. CI - (c) The author(s). FAU - Wang, Mingming AU - Wang M AD - Department of Cell Biology and Genetics, Medical College of Yan'an University, Yan'an 716000, Shaanxi Province, China. FAU - Zhang, Yufu AU - Zhang Y AD - Department of Hepatobiliary Surgery, Affiliated Hospital of Yan'an University, Yan'an 716000, Shaanxi Province, China. FAU - Liu, Min AU - Liu M AD - Department of Pathology, Affiliated Hospital of Yan'an University, Yan'an 716000, Shaanxi Province, China. FAU - Jia, Yuna AU - Jia Y AD - Department of Cell Biology and Genetics, Medical College of Yan'an University, Yan'an 716000, Shaanxi Province, China. FAU - He, Jing AU - He J AD - Laboratory of Obstetrics and Gynecology, Affiliated Hospital of Yan'an University, Yan'an, 716000 Shaanxi Province, China. FAU - Xu, Xiangrong AU - Xu X AD - Department of Cell Biology and Genetics, Medical College of Yan'an University, Yan'an 716000, Shaanxi Province, China. FAU - Shi, Haiyan AU - Shi H AD - Department of Cell Biology and Genetics, Medical College of Yan'an University, Yan'an 716000, Shaanxi Province, China. FAU - Zhang, Yunqing AU - Zhang Y AD - Laboratory of Obstetrics and Gynecology, Affiliated Hospital of Yan'an University, Yan'an, 716000 Shaanxi Province, China. FAU - Zhang, Jing AU - Zhang J AD - Department of Cell Biology and Genetics, Medical College of Yan'an University, Yan'an 716000, Shaanxi Province, China. FAU - Liu, Yusi AU - Liu Y AD - Department of Cell Biology and Genetics, Medical College of Yan'an University, Yan'an 716000, Shaanxi Province, China. LA - eng PT - Journal Article DEP - 20230227 PL - Australia TA - J Cancer JT - Journal of Cancer JID - 101535920 PMC - PMC10088538 OTO - NOTNLM OT - IL-6/JAK2/STAT3 signaling pathway OT - glioblastoma OT - human umbilical cord mesenchymal stem cell supernatant COIS- Competing Interests: The authors have declared that no competing interest exists. EDAT- 2023/04/15 06:00 MHDA- 2023/04/15 06:01 PMCR- 2023/01/01 CRDT- 2023/04/14 02:39 PHST- 2022/08/10 00:00 [received] PHST- 2023/01/17 00:00 [accepted] PHST- 2023/04/15 06:01 [medline] PHST- 2023/04/14 02:39 [entrez] PHST- 2023/04/15 06:00 [pubmed] PHST- 2023/01/01 00:00 [pmc-release] AID - jcav14p0611 [pii] AID - 10.7150/jca.77905 [doi] PST - epublish SO - J Cancer. 2023 Feb 27;14(4):611-627. doi: 10.7150/jca.77905. eCollection 2023.