Department of Gastroenterology, Affiliated Tai Zhou Hospital of Wenzhou Medical University, No.150 Ximen Road, Linhai City, Taizhou 317000, China.
Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
Biomed Res Int. 2020 Mar 8;2020:9259852. doi: 10.1155/2020/9259852. eCollection 2020.
Isoliquiritigenin (ILQ) is a natural product isolated from licorice root which has served as traditional Chinese medicine for a long time. Recently, the antitumor effects of ILQ have been widely studied in various cancers, but the role and related mechanisms of ILQ in esophageal squamous carcinoma cells (ESCC) are still poorly understood. In our studies, ILQ showed profound antitumor activities in ESCC cells. In vitro, ILQ substantially inhibited cell proliferation and anchorage-independent growth in a panel of human ESCC cells. Mechanism studies showed that EGFR signaling pathway played an important role for ILQ to exert its antitumor activity in ESCC. Exposure to isoliquiritigenin substantially decreased EGF-induced EGFR activation and its downstream Akt and ERK1/2 signaling pathway. EGFR knockdown with shRNA in ESCC cell significantly reduced the sensitivity of cancer cells to ILQ. Moreover, it was found that ILQ had a significantly inhibitory effect on AP-1 family, the protein of Jun and Fos subfamilies was substantially downregulated, and the transcriptional activity of AP-1 family was dramatically suppressed by ILQ. By reducing the expression of cyclin D1, ESCC cells were induced G0/G1 arrest, and cell division was substantially blocked. Finally, the antitumor potency of ILQ was validated in xenograft models and the tumor growth was prominently restrained by ILQ. Briefly, our study showed that ILQ, or its analogue, appeared to be a promising new therapeutic agent for ESCC management.
异甘草素（ILQ）是从甘草根中分离出来的天然产物，长期以来一直被用作中药。最近，ILQ 在各种癌症中的抗肿瘤作用已得到广泛研究，但 ILQ 在食管鳞状细胞癌（ESCC）中的作用和相关机制仍知之甚少。在我们的研究中，ILQ 对 ESCC 细胞表现出显著的抗肿瘤活性。在体外，ILQ 显著抑制了一系列人 ESCC 细胞的增殖和锚定非依赖性生长。机制研究表明，EGFR 信号通路在 ILQ 发挥其在 ESCC 中的抗肿瘤活性中起重要作用。暴露于异甘草素可显著降低 EGF 诱导的 EGFR 激活及其下游 Akt 和 ERK1/2 信号通路。用 shRNA 在 ESCC 细胞中敲低 EGFR 可显著降低癌细胞对 ILQ 的敏感性。此外，还发现 ILQ 对 AP-1 家族具有显著的抑制作用，Jun 和 Fos 亚家族的蛋白表达显著下调，ILQ 显著抑制了 AP-1 家族的转录活性。通过降低细胞周期蛋白 D1 的表达，ESCC 细胞被诱导 G0/G1 期阻滞，细胞分裂被显著阻断。最后，在异种移植模型中验证了 ILQ 的抗肿瘤效力，ILQ 显著抑制了肿瘤生长。总之，我们的研究表明，ILQ 或其类似物似乎是 ESCC 治疗的一种很有前途的新治疗剂。
