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:Effects of albumin-bound paclitaxel combined with Sophora subprostrate polysaccharide on inflammatory factors and immune function in breast cancer rats.
Effects of albumin-bound paclitaxel combined with Sophora subprostrate polysaccharide on inflammatory factors and immune function in breast cancer rats.
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肿瘤的发生和生长与炎症程度和免疫活性高度相关。降低荷瘤机体炎症水平以解除免疫抑制、增强抗肿瘤免疫功能,已成为肿瘤治疗的重要策略。
探讨白蛋白结合型紫杉醇联合山豆根多糖(SSP)对荷瘤大鼠抑制炎症、减轻免疫抑制、增强抗肿瘤免疫功能及延缓肿瘤进展的影响,为联合药物在肿瘤中的临床应用提供一定的科学依据。
将大鼠随机分为3组:正常对照组、模型组和药物治疗组。药物干预结束后,取出肿瘤并称重,观察大鼠肿瘤生长情况。采用Western blot检测实验大鼠局部肿瘤组织中肿瘤坏死因子(TNF-α)、白细胞介素(IL)1β、IL-10、穿孔素和颗粒酶B的表达。测定精氨酸酶-1(Arg-1)和环氧合酶2(COX-2)的蛋白表达水平。采用HE染色观察肿瘤炎症浸润情况。使用流式细胞术评估局部肿瘤组织中抗肿瘤免疫细胞——CD8+ T细胞、NK细胞以及免疫抑制细胞的比例。此外,将正常大鼠脾脏T细胞与模型组和联合治疗组荷瘤大鼠脾脏髓源性抑制细胞(MDSC)共培养。使用Cell Trace Far Red检测T细胞增殖,采用流式细胞术通过CD25表达测定T细胞活化水平,并检测荷瘤大鼠体内免疫抑制情况。
联合治疗组与模型组相比,肿瘤重量显著下降。干预后,肿瘤组织附近的 TNF-α 和 IL-1p 水平降低,但抗炎细胞因子 IL-10 水平未发生显著变化。HE 染色结果显示,干预组肿瘤的炎症浸润程度低于模型组。干预后,局部肿瘤组织中 CD8+ T 细胞和 NK 细胞的比例升高。此外,干预组穿孔素和颗粒酶 B 的蛋白表达水平显著高于模型组。在邻近肿瘤组织中存在大量 MDSC。干预后,局部肿瘤组织中 MDSC 的比例显著降低,MDSC 的扩增减少。此外,干预组肿瘤特异性组织中 COX-2 和 Arg-1 的蛋白表达水平显著低于模型组。体外共培养结果表明,联合组大鼠的 T 细胞增殖和活化水平高于模型组动物。
白蛋白结合型紫杉醇联合山豆根多糖可降低局部炎症水平,促进CDB+ T细胞和NK细胞比例及细胞杀伤功能,降低MDSC比例和免疫抑制水平,增强荷瘤小鼠的抗肿瘤免疫功能,并减缓肿瘤生长。
Tumor occurrence and growth are highly correlated with the degree of inflammation and immunological activity. Reducing the level of inflammation in tumor-bearing body to relieve immune suppression and enhance anti-tumor immune function has become an important strategy for tumor treatment.
To investigate the effect of albumin-bound paclitaxel combined with Sophora subprostrate polysaccharide (SSP) on inhibiting inflammation, reducing immunosuppression, enhancing anti-tumor immune function and slowing the progression of tumor in tumor-bearing rats, and to provide certain scientific basis for the clinical application of combined drugs in tumor.
The rats were put into three groups at random: normal control, model group, and drug treatment group. After the end of drug intervention, the tumor was taken out and weighed to observe the tumor growth of the rats. Tumor necrosis factor (TNF-α), interleukin (IL) 1β, IL-10, perforin, and granzyme B were found by Western blot in the local tumor tissues of experimental rats. The protein expression levels of Arginase-1 (Arg-1) and Cyclooxygenase 2 (COX-2) were determined. HE staining was used to observe the inflammatory infiltration of the tumor. Using flow cytometry, the proportions of anti-tumor immune cells-CD8 + T cells, NK cells, and immunosuppressive cells-in local tumor tissues were evaluated. In addition, spleen T cells isolated from normal rats were co-cultured with spleen myeloid derived suppressor cells (MDSC) from tumor-bearing rats in the model group and the combined treatment group. Cell Trace Far Red was used to identify T cell proliferation, flow cytometry was used to determine the level of T cell activation from CD25 expression, and in vivo immunosuppression in tumor-bearing rats was examined.
The combined therapy group experienced a considerable decrease in tumor weight as compared to the model group. TNF-α and IL-1p levels in the vicinity of the tumor tissues reduced following intervention, although IL-10 levels, which are anti-inflammatory cytokines, did not significantly change. The results of the HE staining revealed that the intervention group's tumor had less inflammatory infiltration than the model group did. After intervention, the percentages of CD8 + T cells and NK cells in local tumor tissues increased. Additionally, the intervention group's levels of protein expression for perforin and granzyme B were considerably higher than those of the model group. In the nearby tumor tissues, there were lots of MDSC. Following the intervention, the proportion of MDSC in the local tumor tissues was significantly reduced, and the expansion of MDSC was reduced. Additionally, the intervention group's COX-2 and Arg-1 protein expression levels in the tumor-specific tissues were significantly lower than those of the model group. The outcomes of in vitro co-culture demonstrated that rats in the combination group had higher levels of T cell proliferation and activation than animals in the model group.
Albumin-bound paclitaxel combined with Sophora subprostrate polysaccharide can reduce the local inflammation level, promote the proportion of CDB + T cells and NK cells and cell killing function, reduce the proportion of MDSC and immunosuppressive level, enhance the anti-tumor immune function of tumor-bearing mice, and slow the growth of tumors.
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