CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
我们的工作确立了CD81作为连接放射抵抗与免疫逃逸的关键桥梁,其通过维持GBM中CD274的丰度发挥作用,并突显CD81作为优化放射免疫治疗的有前景的治疗靶点。
英文原题:Mesenchymal Stem Cell-Conditioned Media-Derived Exosomes Loaded With Grifola frondosa Extract Inhibit Lung Cancer via NF-κB and MAPK Pathway Modulation.
Mesenchymal Stem Cell-Conditioned Media-Derived Exosomes Loaded With Grifola frondosa Extract Inhibit Lung Cancer via NF-κB and MAPK Pathway Modulation.
耐药性的日益普遍削弱了化疗及其他治疗方式对肺癌患者的疗效。
耐药日益普遍,降低了肺癌患者化疗及其他治疗方式的疗效,因此亟需开发新治疗方法。本研究考察含灰树花(Grifola frondosa)提取物的间充质干细胞来源外泌体对肺癌细胞的影响。研究者从 MSC 获取外泌体,并通过超声加载灰树花提取物(提取物-外泌体)。体外评估其对 A549 肺癌细胞活率、克隆形成、线粒体膜破坏、迁移、凋亡、自噬和细胞周期的影响,并通过实时 PCR 检测凋亡相关基因 mRNA 表达,采用 Western blot 评估 NF-κB 和 MAPK 信号通路。结果显示,提取物-外泌体显著抑制肺癌细胞增殖、克隆形成和迁移,还增加线粒体膜破坏、凋亡和自噬。处理后处于 G1 和亚 G1 期的癌细胞数量也明显增加。研究结果表明,提取物-外泌体可通过诱导凋亡和自噬、阻滞细胞周期以及调节 NF-κB 和 MAPK 通路,抑制肺癌细胞增殖。
The increasing prevalence of drug resistance diminishes the efficacy of chemotherapy and other therapeutic modalities for individuals diagnosed with lung cancer. Therefore, it is imperative to develop novel treatment approaches. This study examined how mesenchymal stem cell-derived exosomes containing extraction of Grifola frondosa ( G. frondosa ) affected lung cancer cells. Exosomes were obtained from mesenchymal stem cells and loaded with G. frondosa extract (extract-exosomes) by sonication. The effects of extract-exosomes on A549 lung cancer cells were assessed in vitro on cell viability, colony formation, mitochondrial membrane disruption, migration, apoptosis, autophagy, and cell cycle. Moreover, we examined apoptosis-related genes mRNA expression by real-time PCR. Finally, both NF- B and MAPK signaling pathways were evaluated by western blotting method. Our results indicated that exposure to extract-exosomes significantly inhibits lung cancer cells proliferation, colony formation, and migration. Furthermore, this treatment increased mitochondrial membrane disruption, apoptosis, and autophagy in the cancer cells. Additionally, there was a notable increase in the number of the treated cancer cells at G1 and sub-G1 phases of the cell cycle. The research findings indicate that extract-exosomes can inhibit lung cancer cells proliferation through the induction of apoptosis and autophagy, cell cycle arrest, as well as modification of NF- B and MAPK pathways.
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