Li Hongchun, Chen Miao, Yang Zhuying, Wang Qinxian, Wang Jiesheng, Jin Dong, Yang Xiuyun, Chen Fuxing, Zhou Xiumin, Luo Kexue
Department of Cadre Health, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang, People's Republic of China.
Department of Oncology, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang, People's Republic of China.
Onco Targets Ther. 2020 Apr 3;13:2833-2842. doi: 10.2147/OTT.S238958. eCollection 2020.
Pancreatic cancer (PC) is one of the leading causes of cancer, with the lowest 5-year survival rate of all cancer types. Given the fast metastasis of PC and its resistance to surgery, radiotherapy, chemotherapy, and combinations thereof, it is imperative to develop more effective anti-PC drugs. Phillygenin (PHI) has been reported to exert anti-cancer, anti-bacterial, and anti-inflammatory properties. However, the mechanism of PHI in the development of PC is still unclear.
The cytotoxicity of PHI in pancreatic cancer cells was evaluated by MTT assay, and clonogenic assay was used to test the anti-proliferation of PHI. The pro-apoptotic effect of PHI was detected by flow cytometry analysis. The changes of epithelial-mesenchymal transition (EMT) in pancreatic cancer cells treated with PHI were determined by Western blot. Transwell assay was used to test the migration and invasion of PC cells after treatment with PHI. Molecular docking was used to predict the potential binding site of candidate target with PHI.
PHI could inhibit the proliferation, migration, and EMT of PC cells (PANC-1 and SW1990) and induce its apoptosis. Analysis of the Cancer Genome Atlas database indicated that elevated MELK levels correlated with poor overall survival (OS) and disease-free survival (DFS) of PC patients. In addition, molecular modeling showed that PHI may potentially target the catalytic domain of maternal embryonic leucine zipper kinase (MELK). Overexpression of MELK muted the anti-PC effects of PHI.
PHI holds promise as a potent candidate drug for the treatment of PC via targeted MELK.
胰腺癌（PC）是癌症的主要病因之一，是所有癌症类型中5年生存率最低的。鉴于胰腺癌的快速转移及其对手术、放疗、化疗及其联合治疗的耐药性，开发更有效的抗胰腺癌药物势在必行。据报道，连翘酯苷（PHI）具有抗癌、抗菌和抗炎特性。然而，PHI在胰腺癌发生发展中的作用机制仍不清楚。
采用MTT法评估PHI对胰腺癌细胞的细胞毒性，并用克隆形成试验检测PHI的抗增殖作用。通过流式细胞术分析检测PHI的促凋亡作用。用蛋白质免疫印迹法检测PHI处理后胰腺癌细胞上皮-间质转化（EMT）的变化。采用Transwell试验检测PHI处理后胰腺癌细胞的迁移和侵袭能力。用分子对接预测候选靶点与PHI的潜在结合位点。
PHI可抑制胰腺癌细胞（PANC-1和SW1990）的增殖、迁移和EMT并诱导其凋亡。癌症基因组图谱数据库分析表明，MELK水平升高与胰腺癌患者较差的总生存期（OS）和无病生存期（DFS）相关。此外，分子模拟显示PHI可能潜在靶向母源胚胎亮氨酸拉链激酶（MELK）的催化结构域。MELK的过表达减弱了PHI的抗胰腺癌作用。
PHI有望成为一种通过靶向MELK治疗胰腺癌的有效候选药物。
