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:The in vitro treatment of mesenchymal stem cells for colorectal cancer cells.
The in vitro treatment of mesenchymal stem cells for colorectal cancer cells.
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结直肠癌是胃肠道最常见的肿瘤,传统治疗方案给患者和临床医生均带来诸多困难。近年来,由于间充质干细胞(MSC)具有向肿瘤部位迁移的能力,已成为细胞治疗领域的新关注点。
本研究旨在评估MSC对结直肠癌细胞系的促凋亡作用。研究选择HCT-116和HT-29结直肠癌细胞系,并以人脐带血和华通胶作为MSC来源。为区分MSC对癌细胞的作用,还将外周血单个核细胞(PBMC)用作健康对照。脐带血MSC和PBMC通过Ficoll-Paque密度梯度法获取,华通胶MSC则采用组织块贴壁法分离。采用Transwell共培养系统,以癌细胞或PBMC与MSC按1:5或1:10比例共培养24或72小时。通过流式细胞术采用Annexin V/PI-FITC凋亡检测法评估凋亡,并用ELISA检测半胱天冬酶-3和HTRA2/Omi蛋白。结果发现,对于两种癌细胞及两种共培养比例,华通胶MSC在共培养72小时时的促凋亡作用显著更强(p<0.006);而脐带血MSC在共培养24小时时作用更强(p<0.007)。
本研究显示,人脐带血和组织来源MSC处理可诱导结直肠癌细胞凋亡。进一步的体内研究有望阐明MSC的促凋亡作用。
Colorectal cancer is the most common tumor of the gastrointestinal system. The conventional treatment options for colorectal cancer are troublesome for both patients and clinicians. Recently, mesenchymal stem cells (MSCs) have been the novel focus for cell therapy due to their migration to tumor sites. In this study, the apoptotic effect of MSCs on colorectal cancer cell lines has been aimed. HCT-116 and HT-29 were selected as the colorectal cancer cell lines. Human umbilical cord blood and Wharton's jelly were used as mesenchymal stem cell sources. To discriminate against the apoptotic effect of MSC on cancer, we also used peripheral blood mononuclear cells (PBMC) as a healthy control group.
Cord blood-MSC and PBMC were obtained by ficoll-paque density gradient, and Wharton's jelly-MSC by explant method. Transwell co-culture systems were used as cancer cells or PBMC/MSCs at ratios of 1/5 and 1/10, with incubation times of 24 h and 72 h. The Annexin V/PI-FITC-based apoptosis assay was performed by flow cytometry. Caspase-3 and HTRA2/Omi proteins were measured by ELISA.
For both ratios in both cancer cells, it was found that the apoptotic effect of Wharton's jelly-MSC was significantly higher in 72-h incubations (p < 0. 006), whereas the effect of cord blood mesenchymal stem cell in 24-h incubations were higher (p < 0. 007). In this study, we showed that human cord blood and tissue-derived MSCs treatment led to colorectal cancers to apoptosis.
We anticipate that further in vivo studies may shed light on the apoptotic effect of MSC.
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