Wang Mingming, Zhang Yufu, Liu Min, Jia Yuna, He Jing, Xu Xiangrong, Shi Haiyan, Zhang Yunqing, Zhang Jing, Liu Yusi
Department of Cell Biology and Genetics, Medical College of Yan'an University, Yan'an 716000, Shaanxi Province, China.
Department of Hepatobiliary Surgery, Affiliated Hospital of Yan'an University, Yan'an 716000, Shaanxi Province, China.
J Cancer. 2023 Feb 27;14(4):611-627. doi: 10.7150/jca.77905. eCollection 2023.
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. 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. The results demonstrated that after treatment with HUC-MSCs supernatants, 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. 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.
我们研究了人脐带间充质干细胞(HUC-MSCs)上清液对胶质母细胞瘤(GBM)细胞系RG-2、U251、U87-MG和LN-428增殖、迁移、侵袭及凋亡的影响,以及通过IL-6/JAK2/STAT3信号通路介导的细胞凋亡和自噬,以探索其分子机制。在本研究中,用9mg/ml的HUC-MSCs上清液处理RG-2、U251、U87-MG和LN-428细胞。通过多种实验方法分析它们对HUC-MSCs上清液处理的反应以及STAT3信号的状态,以阐明HUC-MSCs上清液对GBM的重要性。结果表明,用HUC-MSCs上清液处理后,RG-2、U251、U87-MG和LN-428细胞的增殖受到抑制,其持续生长也被阻断。RG-2、U251和U87-MG细胞出现明显的S期积累,而LN-428细胞被阻滞在G0/G1期。它们的迁移侵袭能力受到抑制,凋亡和自噬比例增加。这些作用是通过IL-6/JAK2/STAT3及其下游信号通路介导的。我们的数据表明,HUC-MSCs上清液对GBM细胞具有抗肿瘤作用。它抑制了GBM细胞的增殖、迁移和侵袭,并促进了它们的凋亡。IL-6/JAK2/STAT3信号通路的负调控增强了肿瘤细胞的凋亡和自噬,从而提高了对GBM的治疗效果。