■尽管治疗取得了进展,癌症死亡的主要原因之一仍然是肺癌。为了改善目前的治疗或预防非小细胞肺癌(NSCLC),需要更详细地了解营养在癌症发病和进展中的作用。而在结肠直肠癌中,已经很好地研究了局部微生物群衍生的SCFA的影响,应更深入地研究SCFA通过外周血免疫系统对肺癌细胞的影响。在这方面,通过肠道吸收的营养物质可能会影响肿瘤微环境(TME),从而在肿瘤细胞生长中起重要作用。
■这项研究的重点是短链脂肪酸(SCFA)丁酸钠(SB)的影响,肺癌细胞存活。我们先前描述了葡萄糖对A549肺腺癌细胞系的促肿瘤作用。在这项研究中,我们想知道SB是否会抵消葡萄糖的作用,从而在存在或不存在葡萄糖的情况下体外培养A549和H520,并研究SB治疗如何影响肺癌细胞的存活及其对免疫细胞对抗肺癌的影响.
■在这项研究中,我们用A549,H520和NSCLC患者来源的上皮细胞在不同SB水平下进行了细胞培养实验.为了研究对免疫系统的影响,我们从对照组进行了外周血单核细胞(PBMC)的体外培养,吸烟者和肺癌患者SB浓度增加。
■为了研究SB对肺肿瘤细胞的影响,我们首先分析了6种不同浓度的SB在细胞培养48和72小时对A549细胞的影响。在这里我们发现,SB治疗以浓度依赖性方式降低肺癌细胞存活。接下来我们更深入地分析了这两种浓度,这导致了细胞存活率的最大降低。这里,我们观察到SB导致A549肺癌细胞的细胞周期停滞和诱导早期凋亡。诱导细胞周期调控蛋白和A549肺癌干细胞标志物(CD90)的表达。此外,本研究探讨干扰素-γ(IFN-γ)及其受体(IFN-γ-R1)联合SB治疗的作用,揭示了这一点,虽然IFN-γ-R1表达增加,IFN-γ不影响SB降低肿瘤细胞活力的功效。此外,我们研究了SB对免疫细胞的影响,特别是健康个体的CD8+T细胞和自然杀伤(NK)细胞,吸烟者,NSCLC患者。SB处理导致CD8+T细胞和NK细胞中IFN-γ和颗粒酶B的产生减少。此外,在来自对照和NSCLC受试者的PBMC中,在不存在葡萄糖的情况下,SB在NK细胞和CD4+T细胞中诱导IFN-γ-R1。
■总的来说,这项研究强调了SB抑制肺癌细胞生长的潜力,触发细胞凋亡,诱导细胞周期停滞,通过激活外周血CD4+T细胞调节免疫应答,同时选择性诱导外周血NK细胞中的IFN-γ-R1,抑制外周血CD8+T细胞和NK细胞。因此,了解SB在TME中的作用机制及其对免疫系统的影响,可为可能将SB视为NSCLC辅助治疗的候选药物提供有价值的见解.
UNASSIGNED: Despite therapy advances, one of the leading causes of cancer deaths still remains lung cancer. To improve current treatments or prevent non-small cell lung cancer (NSCLC), the role of the nutrition in cancer onset and progression needs to be understood in more detail. While in colorectal cancer, the influence of local microbiota derived SCFAs have been well investigated, the influence of SCFA on lung cancer cells via peripheral blood immune system should be investigated more deeply. In this respect, nutrients absorbed via the gut might affect the tumor microenvironment (TME) and thus play an important role in tumor cell growth.
UNASSIGNED: This study focuses on the impact of the short-chain fatty acid (SCFA) Sodium Butyrate (SB), on lung cancer cell survival. We previously described a pro-tumoral role of glucose on A549 lung adenocarcinoma cell line. In this study, we wanted to know if SB would counteract the effect of glucose and thus cultured A549 and H520 in vitro with and without SB in the presence or absence of glucose and investigated how the treatment with SB affects the survival of lung cancer cells and its influence on immune cells fighting against lung cancer.
UNASSIGNED: In this study, we performed cell culture experiments with A549, H520 and NSCLC-patient-derived epithelial cells under different SB levels. To investigate the influence on the immune system, we performed in vitro culture of peripheral mononuclear blood cells (PBMC) from control, smoker and lung cancer patients with increasing SB concentrations.
UNASSIGNED: To investigate the effect of SB on lung tumor cells, we first analyzed the effect of 6 different concentrations of SB on A549 cells at 48 and 72 hours cell culture. Here we found that, SB treatment reduced lung cancer cell survival in a concentration dependent manner. We next focused our deeper analysis on the two concentrations, which caused the maximal reduction in cell survival. Here, we observed that SB led to cell cycle arrest and induced early apoptosis in A549 lung cancer cells. The expression of cell cycle regulatory proteins and A549 lung cancer stem cell markers (CD90) was induced. Additionally, this study explored the role of interferon-gamma (IFN-γ) and its receptor (IFN-γ-R1) in combination with SB treatment, revealing that, although IFN-γ-R1 expression was increased, IFN-γ did not affect the efficacy of SB in reducing tumor cell viability. Furthermore, we examined the effects of SB on immune cells, specifically CD8+ T cells and natural killer (NK) cells from healthy individuals, smokers, and NSCLC patients. SB treatment resulted in a decreased production of IFN-γ and granzyme B in CD8+ T cells and NK cells. Moreover, SB induced IFN-γ-R1 in NK cells and CD4+ T cells in the absence of glucose both in PBMCs from controls and NSCLC subjects.
UNASSIGNED: Overall, this study highlights the potential of SB in inhibiting lung cancer cell growth, triggering apoptosis, inducing cell cycle arrest, and modulating immune responses by activating peripheral blood CD4+ T cells while selectively inducing IFN-γ-R1 in NK cells in peripheral blood and inhibiting peripheral blood CD8+ T cells and NK cells. Thus, understanding the mechanisms of action of SB in the TME and its influence on the immune system provide valuable insights of potentially considering SB as a candidate for adjunctive therapies in NSCLC.