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:Olive Leaf Extract Enhances Natural Killer Cell-Mediated Cytotoxicity against Colorectal Cancer Cells.
Olive Leaf Extract Enhances Natural Killer Cell-Mediated Cytotoxicity against Colorectal Cancer Cells.
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我们的研究结果表明,OLE 在较低且生理可达到的剂量下可通过 NK 细胞引发强效抗癌反应。
自然杀伤(NK)细胞是通过穿孔素/颗粒酶介导细胞毒作用清除恶性细胞的先天淋巴细胞。本研究探讨富含橄榄苦苷和羟基酪醇的橄榄叶提取物(OLE)能否增强NK细胞对结直肠癌(CRC)细胞的细胞毒性。尽管OLE具有直接抗癌作用,但其治疗应用受生物利用度较低的限制,直接细胞毒作用需要超生理浓度。
在共培养模型中评估OLE对NK-92细胞杀伤HT-29结直肠癌细胞活性的影响。
采集土耳其巴勒克埃西尔的橄榄叶,经干燥后用70%甲醇提取。采用MTT和ATP检测评估OLE对HT-29细胞及NK-92细胞活力的影响。此外,在直接共培养体系中评估NK-92细胞对HT-29细胞的细胞毒活性,并采用ELISA试剂盒测定颗粒酶B和穿孔素水平。
OLE以剂量依赖方式抑制HT-29细胞增殖,IC值为548 μg/mL。低浓度OLE(100–200 μg/mL)促进NK-92细胞增殖,而较高浓度则产生细胞毒性。在共培养实验中,添加无毒浓度的OLE(100和200 μg/mL)显著增强NK-92细胞对HT-29细胞的杀伤作用。OLE处理后颗粒酶B和穿孔素水平显著升高,进一步支持细胞毒性增强。
我们的结果提示,在较低且生理上可达到的剂量下,OLE可通过NK细胞产生强效抗癌反应。这些发现凸显了利用OLE免疫调节作用增强先天抗肿瘤防御、治疗CRC的潜在策略。
Natural Killer (NK) cells are innate lymphoid cells that eliminate malignant cells via perforin/granzyme-mediated cytotoxicity. This study investigates whether Olive Leaf Extract (OLE), rich in oleuropein and hydroxytyrosol, can enhance NK-cell cytotoxicity against colorectal cancer (CRC) cells. Although OLE exhibits direct anticancer effects, its therapeutic utility is constrained by poor bioavailability, requiring supraphysiological concentrations for direct cytotoxicity.
To evaluate the effect of OLE on the cytotoxic activity of NK-92 cells against HT-29 colorectal cancer cells within a co-culture model.
Olive leaves obtained from Bal kesir, T rkiye were dried and extracted with 70% methanol. The effects of OLE on the viability of HT-29 cells and NK-92 cells were evaluated using MTT and ATP assays. Additionally, the cytotoxic activity of NK-92 cells against HT-29 cells was assessed in a direct co-culture system. Granzyme B and perforin levels were measured using ELISA kits.
OLE inhibited the proliferation of HT-29 cells in a dose-dependent manner, with an IC values of 548 g/mL. In NK-92 cells, low concentrations of OLE (100-200 g/mL) promoted cell proliferation, whereas higher concentrations exerted cytotoxic effects. In co-culture experiments, NK-92-mediated cytotoxicity against HT-29 cells was significantly enhanced by the addition of OLE at non-toxic concentrations (100 and 200 g/mL). This enhanced cytotoxicity was further supported by a significant increase in granzyme B and perforin levels following OLE treatment.
Our findings suggest that OLE can elicit a potent anticancer response via NK cells at lower, physiologically achievable doses. These results highlight a promising therapeutic strategy for CRC, leveraging OLE's immunomodulatory effects to enhance innate antitumor defenses.
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