富含氰-3-O-糖苷的黑米部分减弱IL-1β/IL-6驱动的A549肺癌细胞迁移和侵袭,并调节JAK1/STAT3信号传导

Cyanidin-3-O-Glucoside-Rich Black Rice Fraction Attenuates IL-1β/IL-6-Driven A549 Lung Cancer Cell Migration and Invasion and Modulates JAK1/STAT3 Signaling.

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摘要(中文译文)

肿瘤微环境中的炎症介质通过细胞因子依赖性信号网络增强细胞运动能力和侵袭能力,从而促进肺癌进展。膳食生物活性化合物对这些炎症相关通路的调节可能为限制癌症侵袭性提供补充策略。本研究旨在探讨富含矢车菊素-3-O-葡萄糖苷(cyanidin-3-O-glucoside,C3G)的Kum Akha色素黑米组分(CKAB-P1)对炎症刺激下A549癌细胞进展的抑制作用。CKAB-P1通过溶剂分配萃取获得,并采用pH示差法和高性能液相色谱法进行化学表征。A549细胞经CKAB-P1或C3G预处理后,再用主要含有IL-6和IL-1β的条件培养基(来源于LPS暴露的THP-1巨噬细胞,即THP-1-CS)进行刺激。采用划痕愈合实验、Transwell侵袭实验、明胶酶谱分析和Western blot分析评估对癌细胞迁移和侵袭的影响。CKAB-P1中总花青素含量为106.62 ± 3.54 mg/g提取物,其中C3G为主要成分(59.42 ± 2.54 mg/g提取物)。THP-1-CS暴露可促进A549肺癌细胞的迁移和侵袭,而中和IL-6和IL-1β可减弱这些促迁移效应,证实了细胞因子的参与。CKAB-P1(10-40 μg/mL)或C3G(2.5-20 μg/mL)处理可显著减弱炎症增强的迁移和侵袭( < 0.05)。同时观察到MMP-2和MMP-9活性降低,以及侵袭相关蛋白(uPA、uPAR和MT1-MMP)表达下降。此外,CKAB-P1和C3G均可减弱JAK1和STAT3的磷酸化。这些研究结果表明,富含花青素的黑米组分可能通过调节细胞因子驱动的JAK1/STAT3信号级联来限制炎症驱动的A549肺癌细胞侵袭性,提示其作为靶向肿瘤相关炎症信号的生物活性膳食成分具有潜在相关性。

Abstract

Inflammatory mediators within the tumor microenvironment contribute to lung cancer progression by enhancing cellular motility and invasive capacity through cytokine-dependent signaling networks. Modulation of these inflammation-associated pathways by dietary bioactive compounds may provide complementary strategies for limiting cancer aggressiveness. Our objective was to examine the inhibitory effects of a cyanidin-3-O-glucoside (C3G)-rich fraction from Kum Akha pigmented black rice (CKAB-P1) on inflammation-stimulated A549 cancer cell progression. CKAB-P1 was obtained through solvent-partition extraction and chemically characterized using the pH differential method and high-performance liquid chromatography. A549 cells were pretreated with CKAB-P1 or C3G, followed by stimulation with conditioned medium predominantly containing IL-6 and IL-1β derived from LPS-exposed THP-1 macrophages (THP-1-CS). Effects on cancer cell migration and invasion were evaluated using wound-healing, Transwell invasion, gelatin zymography, and Western blot analyses. CKAB-P1 contained 106.62 ± 3.54 mg/g extract of total anthocyanins, with C3G representing the major constituent (59.42 ± 2.54 mg/g extract). Exposure of THP-1-CS stimulated migration and invasion of A549 lung cancer, and neutralization of IL-6 and IL-1β reduced these pro-migratory effects, confirming cytokine involvement. Treatment with CKAB-P1 (10-40 μg/mL) or C3G (2.5-20 μg/mL) markedly attenuated inflammation-enhanced migration and invasion ( < 0.05). A reduction in MMP-2 and MMP-9 activity, along with decreased expression of invasion-associated protein expressions (uPA, uPAR, and MT1-MMP), was observed. Furthermore, both CKAB-P1 and C3G attenuated phosphorylation of JAK1 and STAT3. These findings suggest that anthocyanin-enriched black rice fraction may limit inflammation-driven A549 lung cancer cell aggressiveness through modulation of the cytokine-driven JAK1/STAT3 signaling cascade, indicating its potential relevance as a bioactive dietary component targeting tumor-associated inflammatory signaling.

如何引用

AMA

Warathit Semmarath, Punnida Arjsri, Kamonwan Srisawad, Intranee Intanil, Sansanee Jamjod, Chanakan Prom-U-Thai, et al. Cyanidin-3-O-Glucoside-Rich Black Rice Fraction Attenuates IL-1β/IL-6-Driven A549 Lung Cancer Cell Migration and Invasion and Modulates JAK1/STAT3 Signaling.. Nutrients. 2026; doi:10.3390/nu18081198.

APA

Warathit Semmarath, Punnida Arjsri, Kamonwan Srisawad, Intranee Intanil, Sansanee Jamjod, Chanakan Prom-U-Thai, et al (2026). Cyanidin-3-O-Glucoside-Rich Black Rice Fraction Attenuates IL-1β/IL-6-Driven A549 Lung Cancer Cell Migration and Invasion and Modulates JAK1/STAT3 Signaling.. Nutrients. https://doi.org/10.3390/nu18081198

GB/T 7714

Warathit Semmarath, Punnida Arjsri, Kamonwan Srisawad, Intranee Intanil, Sansanee Jamjod, Chanakan Prom-U-Thai, et al. Cyanidin-3-O-Glucoside-Rich Black Rice Fraction Attenuates IL-1β/IL-6-Driven A549 Lung Cancer Cell Migration and Invasion and Modulates JAK1/STAT3 Signaling.[J]. Nutrients, 2026 doi:10.3390/nu18081198.

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