紫草素是一种从紫草植物中提取的天然萘醌化合物，具有抗肿瘤、抗炎和抗菌特性。细胞衰老在预防肿瘤进展中起着关键作用。目前尚不清楚紫草素是否对结肠癌细胞衰老有影响。在本研究中，我们首先测定了紫草素对结肠癌细胞系HT29和HCT116的IC50值。然后，我们使用细胞计数试剂盒8、集落形成和伤口愈合实验验证了紫草素对结肠癌细胞系HT29和HCT116的增殖和迁移能力的抑制作用。接下来，我们使用高通量 mRNA 测序确定了一系列潜在靶标，并确定了 210 个上调基因和 296 个下调基因。 KEGG 分析揭示了八个与细胞衰老相关的下调基因：CCNB3、IL-1α、CXCL8、CDKN2A、MYC、IGFBP3、SQSTM1 和 GADD45G。其中，CXCL8和CDKN2A与结肠癌患者的不良预后相关，表明紫草素下调它们的表达可以提高患者的生存率。此外，SA-β-半乳糖苷酶染色显示，紫草素处理后结肠癌细胞的细胞衰老百分比显着增加。分子对接显示紫草素通过阻断 CXCL8 活性来抑制结肠癌进展。基于这些发现，我们认为紫草素可能通过下调CDKN2A和CXCL8来诱导结肠癌细胞衰老并发挥抗肿瘤活性。这为紫草素抑制结肠癌进展提供了新的分子机制和潜在的治疗靶点。版权所有©2024 Liu，Zhao，Liu，Wu，Li，Fu，Yang和Liang。

Shikonin, a naturally occurring naphthoquinone compound extracted from comfrey plants, has antitumor, anti-inflammatory, and antimicrobial properties. Cell senescence plays a key role in preventing tumor progression. It is unclear whether shikonin has an effect on cell senescence in colon cancer. In the current study, we first determine the IC50 values of shikonin on colon cancer cell lines HT29 and HCT116. Then, we verified the inhibitory effects of shikonin on the proliferation and migration abilities of colon cancer cell lines HT29 and HCT116 using cell counting kit-8, colony formation, and wound healing assays. Next, we identified a series of potential targets using high-throughput mRNA sequencing and identified 210 upregulated and 296 downregulated genes. KEGG profiling revealed eight downregulated genes associated with cell senescence: CCNB3, IL-1α, CXCL8, CDKN2A, MYC, IGFBP3, SQSTM1, and GADD45G. Among them, CXCL8 and CDKN2A were associated with poor prognosis in patients with colon cancer, suggesting that their downregulation by shikonin could improve patient survival. Furthermore, SA-β-galactosidase staining revealed that the percentage of cellular senescence in colon cancer cells was significantly increased after shikonin treatment. Molecular docking revealed that shikonin suppressed colon cancer progression by blocking CXCL8 activity. Based on these findings, we deem that shikonin might induce senescence and exert antitumor activity in colon cancer cells by downregulating CDKN2A and CXCL8. This provides a new molecular mechanism and potential therapeutic target for shikonin to inhibit colon cancer progression.Copyright © 2024 Liu, Zhao, Liu, Wu, Li, Fu, Yang and Liang.