异甘草素通过下调葡萄糖调节蛋白78抑制胃癌干性、调节肿瘤微环境并抑制肿瘤生长。

Isoliquiritigenin Inhibits Gastric Cancer Stemness, Modulates Tumor Microenvironment, and Suppresses Tumor Growth through Glucose-Regulated Protein 78 Downregulation.

作者信息

Lee Chien-Hsing, Tsai Hsin-Yi, Chen Chun-Lin, Chen Jen-Lung, Lu Chao-Chun, Fang Yi-Ping, Wu Deng-Chyang, Huang Yaw-Bin, Lin Ming-Wei

机构信息

Department of Pharmacology, School of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

Drug Development and Value Creation Research Center, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.

出版信息

Biomedicines. 2022 Jun 8;10(6):1350. doi: 10.3390/biomedicines10061350.

Chemotherapy is the treatment of choice for gastric cancer; however, the currently available therapeutic drugs for treatment have limited efficacy. Cancer stemness and the tumor microenvironment may play crucial roles in tumor growth and chemoresistance. Glucose-regulated protein 78 (GRP78) is an endoplasmic reticulum chaperone facilitating protein folding and cell homeostasis during stress and may participate in chemoresistance. Isoliquiritigenin (ISL) is a bioactive flavonoid found in licorice. In this study, we demonstrated the role of GRP78 in gastric cancer stemness and evaluated GRP78-mediated stemness inhibition, tumor microenvironment regulation, and chemosensitivity promotion by ISL. ISL not only suppressed GRP78-mediated gastric cancer stem cell-like characteristics, stemness-related protein expression, and cancer-associated fibroblast activation but also gastric tumor growth in xenograft animal studies. The findings indicated that ISL is a promising candidate for clinical use in combination chemotherapy.

化疗是胃癌的首选治疗方法；然而，目前可用的治疗药物疗效有限。癌症干性和肿瘤微环境可能在肿瘤生长和化疗耐药中起关键作用。葡萄糖调节蛋白78（GRP78）是一种内质网伴侣蛋白，在应激期间促进蛋白质折叠和细胞稳态，并可能参与化疗耐药。异甘草素（ISL）是一种存在于甘草中的生物活性黄酮类化合物。在本研究中，我们证明了GRP78在胃癌干性中的作用，并评估了ISL对GRP78介导的干性抑制、肿瘤微环境调节和化疗敏感性促进作用。在异种移植动物研究中，ISL不仅抑制了GRP78介导的胃癌干细胞样特征、干性相关蛋白表达和癌症相关成纤维细胞活化，还抑制了胃肿瘤生长。研究结果表明，ISL是联合化疗临床应用的一个有前景的候选药物。