Department of Radiation Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, China.
Department of Radiation Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, China; The Fourth Clinical School of Nanjing Medical University, Nanjing, 210009, China.
Eur J Pharmacol. 2019 Aug 5;856:172352. doi: 10.1016/j.ejphar.2019.04.033. Epub 2019 Apr 17.
Nasopharyngeal Carcinoma is limited by the various severe side-effects and surgery is rarely performed. Iosliquiritigenin has a series of biological activities, such as antiviral, anti-free radical and antitumor. However, the role and underlying mechanism of isoliquiritigenin in nasopharyngeal carcinoma have not been understood yet. Herein, the results revealed that isoliquiritigenin could inhibit cell proliferation in nasopharyngeal carcinoma cell lines, including C666-1 and CNE2, in both Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU) assay. In addition, isoliquiritigenin promoted nasopharyngeal carcinoma cell apoptosis, with the up-regulations of Bax, Caspase-3 and Caspase-9 and the down-regulation of Bcl-2. Meanwhile, isoliquiritigenin suppressed nasopharyngeal carcinoma cells migration and invasion with the down-regulation of matrix metalloproteinases (MMP)-2 and MMP-9. Furthermore, the expression of miR-32 was up-regulated in the nasopharyngeal carcinoma tissues, while isoliquiritigenin could significantly down-regulate the expression of miR-32. And over-expression of miR-32 promoted the nasopharyngeal carcinoma cells growth, migration and invasion, and suppressed apoptosis. However, isoliquiritigenin treatment dramatically inhibited the effect of miR-32. Besides, luciferase reporter assay confirmed that large tumor suppressor 2 (LATS2) was a direct target of miR-32. And isoliquiritigenin increased the expression of LATS2, while silencing of LATS2 promoted the nasopharyngeal carcinoma cells growth. Moreover, western blotting discovered that isoliquiritigenin inhibited nasopharyngeal carcinoma cells growth via Wnt signaling pathway. Finally, CNE2 cells transplanted xenografts tumor model in nude mice were performed and it suggested that isoliquiritigenin could inhibit the development of xenografts nude mice, along with the decrease of tumor volume and the expression of miR-32 and LATS2. Overall, isoliquiritigenin was confirmed to be a potent anti-nasopharyngeal carcinoma compound both in vitro and in vivo, and accomplished by regulation of miR-32/LATS2/Wnt.
鼻咽癌受限于各种严重的副作用，很少采用手术治疗。甘草查尔酮 B 具有抗病毒、抗自由基和抗肿瘤等一系列生物学活性。然而，甘草查尔酮 B 在鼻咽癌中的作用和机制尚不清楚。本研究结果表明，甘草查尔酮 B 可通过细胞计数试剂盒-8 (CCK-8) 和 5-乙炔基-2'-脱氧尿苷 (EdU) 检测抑制鼻咽癌细胞系 C666-1 和 CNE2 的细胞增殖。此外，甘草查尔酮 B 促进鼻咽癌细胞凋亡，上调 Bax、Caspase-3 和 Caspase-9，下调 Bcl-2。同时，甘草查尔酮 B 通过下调基质金属蛋白酶 (MMP)-2 和 MMP-9 抑制鼻咽癌细胞迁移和侵袭。此外，miR-32 在鼻咽癌组织中表达上调，而甘草查尔酮 B 可显著下调 miR-32 的表达。过表达 miR-32 促进鼻咽癌细胞生长、迁移和侵袭，抑制凋亡。然而，甘草查尔酮 B 处理显著抑制了 miR-32 的作用。此外，荧光素酶报告基因检测证实，大肿瘤抑制因子 2 (LATS2) 是 miR-32 的直接靶基因。甘草查尔酮 B 增加 LATS2 的表达，而 LATS2 的沉默促进了鼻咽癌细胞的生长。此外，western blot 发现甘草查尔酮 B 通过 Wnt 信号通路抑制鼻咽癌细胞生长。最后，在裸鼠中进行了 CNE2 细胞移植异种移植肿瘤模型的实验，结果表明甘草查尔酮 B 可抑制异种移植裸鼠肿瘤的发展，同时降低肿瘤体积和 miR-32 和 LATS2 的表达。总的来说，甘草查尔酮 B 在体内外均被证实为一种有效的抗鼻咽癌化合物，其作用机制是通过调节 miR-32/LATS2/Wnt。
