RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Enhanced Anti-Tumor Effects of Natural Killer Cell-Derived Exosomes Through Doxorubicin Delivery to Hepatocellular Carcinoma Cells: Cytotoxicity and Apoptosis Study.
Enhanced Anti-Tumor Effects of Natural Killer Cell-Derived Exosomes Through Doxorubicin Delivery to Hepatocellular Carcinoma Cells: Cytotoxicity and Apoptosis Study.
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外泌体是由多种细胞(包括自然杀伤(NK)细胞)分泌的纳米级细胞外囊泡,以其低毒性、高渗透性、生物相容性和强靶向能力而闻名。NK细胞来源的外泌体(NK-exos)含有增强肿瘤靶向效率的细胞毒性蛋白,使其适合用于治疗肝细胞癌(HCC)等实体瘤。尽管其在药物递送方面具有潜力,但载药NK-exos,特别是载有多柔比星(NK-exos-Dox)的NK-exos,在HCC中的作用机制仍不清楚。
本研究探讨了NK-exos-Dox对Hep3B细胞的体外抗肿瘤作用。NK-exos-Dox表达外泌体标志物(CD9和CD63)和细胞毒性蛋白(颗粒酶B和穿孔素),大小为170-220 nm。与NK-exos相比,NK-exos-Dox通过上调促凋亡蛋白(Bax、细胞色素c、cleaved caspase 3和cleaved PARP)并抑制抗凋亡蛋白(Bcl-2),增强了Hep3B细胞的细胞毒性和凋亡。这些发现表明,NK-exos-Dox通过激活特定的细胞毒性分子显著增强抗肿瘤作用,为包括HCC在内的实体瘤治疗提供了有前景的治疗机会。
Exosomes are nanosized extracellular vesicles secreted by various cells, including natural killer (NK) cells, and are known for their low toxicity, high permeability, biocompatibility, and strong targeting ability.
NK cell-derived exosomes (NK-exos) contain cytotoxic proteins that enhance tumor-targeting efficiency, making them suitable for treating solid tumors such as hepatocellular carcinoma (HCC). Despite their potential in drug delivery, the mechanisms of drug-loaded NK-exos, particularly those loaded with doxorubicin (NK-exos-Dox), remain unclear in HCC.
This study explored the anti-tumor effects of NK-exos-Dox against Hep3B cells in vitro . NK-exos-Dox expressed exosome markers (CD9 and CD63) and cytotoxic proteins (granzyme B and perforin) and measured 170-220 nm in size. Compared to NK-exos, NK-exos-Dox enhanced cytotoxicity and apoptosis in Hep3B cells by upregulating pro-apoptotic proteins (Bax, cytochrome c, cleaved caspase 3, and cleaved PARP) and inhibiting the anti-apoptotic protein (Bcl-2).
These findings suggest that NK-exos-Dox significantly boost anti-tumor effects by activating specific cytotoxic molecules, offering promising therapeutic opportunities for solid tumor treatment, including HCC.
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