Wang Guifeng, Hiramoto Keiichi, Ma Ning, Yoshikawa Nobuji, Ohnishi Shiho, Murata Mariko, Kawanishi Shosuke
Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
Sakuranomori Shiroko Home, Social Service Elderly Facilities, Suzuka University of Medical Science, Suzuka, Mie 513-0816, Japan.
Int J Mol Sci. 2021 Mar 5;22(5):2609. doi: 10.3390/ijms22052609.
Glycyrrhizin (GL), an important active ingredient of licorice root, which weakens the proinflammatory effects of high-mobility group box 1 (HMGB1) by blocking HMGB1 signaling. In this study, we investigated whether GL could suppress inflammation and carcinogenesis in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced murine model of colorectal cancer. ICR mice were divided into four groups ( = 5, each)-control group, GL group, colon cancer (CC) group, and GL-treated CC (CC + GL) group, and sacrificed after 20 weeks. Plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured using an enzyme-linked immunosorbent assay. The colonic tissue samples were immunohistochemically stained with DNA damage markers (8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxy-guanosine), inflammatory markers (COX-2 and HMGB1), and stem cell markers (YAP1 and SOX9). The average number of colonic tumors and the levels of IL-6 and TNF-α in the CC + GL group were significantly lower than those in the CC group. The levels of all inflammatory and cancer markers were significantly reduced in the CC + GL group. These results suggest that GL inhibits the inflammatory response by binding HMGB1, thereby inhibiting DNA damage and cancer stem cell proliferation and dedifferentiation. In conclusion, GL significantly attenuates the pathogenesis of AOM/DSS-induced colorectal cancer by inhibiting HMGB1-TLR4-NF-κB signaling.
甘草甜素（GL）是甘草根的一种重要活性成分，它通过阻断高迁移率族蛋白B1（HMGB1）信号传导来减弱HMGB1的促炎作用。在本研究中，我们调查了GL是否能在氧化偶氮甲烷（AOM）/葡聚糖硫酸钠（DSS）诱导的小鼠结直肠癌模型中抑制炎症和致癌作用。将ICR小鼠分为四组（每组n = 5）——对照组、GL组、结肠癌（CC）组和GL治疗的CC组（CC + GL组），并在20周后处死。使用酶联免疫吸附测定法测量血浆白细胞介素（IL）-6和肿瘤坏死因子（TNF）-α水平。结肠组织样本用DNA损伤标志物（8-硝基鸟嘌呤和8-氧代-7,8-二氢-2'-脱氧鸟苷）、炎症标志物（COX-2和HMGB1）和干细胞标志物（YAP1和SOX9）进行免疫组织化学染色。CC + GL组的结肠肿瘤平均数量以及IL-6和TNF-α水平显著低于CC组。CC + GL组中所有炎症和癌症标志物的水平均显著降低。这些结果表明，GL通过结合HMGB1抑制炎症反应，从而抑制DNA损伤以及癌症干细胞的增殖和去分化。总之，GL通过抑制HMGB1-TLR4-NF-κB信号传导显著减轻AOM/DSS诱导的结直肠癌的发病机制。
