Wu Di, Wang Xin-Ping, Zhang Wei
Department of Hematology, The First Affiliated Hospital of Xi'an Jiaotong University, 710061, China.
Department of General Surgery, GuangRen Hospital of Xi'an Jiaotong University, Xi'an No. 4 Hospital, Xi'an, Shaanxi 710004, China.
Cell Mol Biol (Noisy-le-grand). 2019 Jul 31;65(6):96-100.
Colorectal cancer (CRC) is a common malignant tumor that seriously threatens human health and quality of life. At present, the search for safe and more effective treatment for CRC has become necessary. The present study investigated the anti-proliferative and apoptotic effects of sesamolin on human colorectal cancer (HCT116) cells, and the underlying mechanism. Cell proliferation was determined using MTT assay, while the expressions of JAK2, STAT3 and p-STA3 were determined using Western blotting. The levels of expression of matrix metalloproteinases-1, 2 and 9 (MMP1, MMP2 and MMP9) were determined using real-time quantitative polymerase chain reaction (qRT-PCR). The degree of migration and invasion of the cells was assessed using wound healing assay. The results of MTT assay showed that sesamolin significantly and time- and dose-dependently inhibited the proliferation of HCT116 cells (p < 0.05). Treatment of HCT116 cells with sesamolin significantly inhibited their migratory ability (p < 0.05). The expressions of p-JAK2 and p-STAT3 were significantly down-regulated 48 h after 20 µM of JAK2 specific inhibitor (AG490) was added to HCT116 cells (p < 0.05). The expression of p-STAT3 was also significantly and dose-dependently down-regulated 6 h after treatment of HCT116 cells with sesamolin (p < 0.05). Sesamolin and AG490 had synergistic effect and their combination significantly down-regulated the expression of p-STAT3, when compared with sesamolin alone (p < 0.05). Treatment of HCT116 cells with sesamolin significantly and dose-dependently reduced the levels of IL-6-induced expressions of MMP-1, MMP-2 and MMP-9 (p < 0.05). These results suggest that sesamolin induces apoptosis in HCT116 cells and prevents cell invasion via inhibition of the JAK2/STAT3 signaling pathway.
结直肠癌（CRC）是一种严重威胁人类健康和生活质量的常见恶性肿瘤。目前，寻找安全且更有效的CRC治疗方法已成为必然。本研究调查了芝麻素对人结肠癌细胞（HCT116）的抗增殖和凋亡作用及其潜在机制。采用MTT法测定细胞增殖，用蛋白质印迹法测定JAK2、STAT3和p-STA3的表达。使用实时定量聚合酶链反应（qRT-PCR）测定基质金属蛋白酶-1、2和9（MMP1、MMP2和MMP9）的表达水平。采用伤口愈合试验评估细胞的迁移和侵袭程度。MTT试验结果表明，芝麻素显著且呈时间和剂量依赖性地抑制HCT116细胞的增殖（p<0.05）。用芝麻素处理HCT116细胞可显著抑制其迁移能力（p<0.05）。在向HCT116细胞中加入20µM的JAK2特异性抑制剂（AG490）48小时后，p-JAK2和p-STAT3的表达显著下调（p<0.05）。用芝麻素处理HCT116细胞6小时后，p-STAT3的表达也显著且呈剂量依赖性下调（p<0.05）。芝麻素和AG490具有协同作用，与单独使用芝麻素相比，它们的组合显著下调了p-STAT3的表达（p<0.05）。用芝麻素处理HCT116细胞可显著且呈剂量依赖性地降低IL-6诱导的MMP-1、MMP-2和MMP-9的表达水平（p<0.05）。这些结果表明，芝麻素通过抑制JAK2/STAT3信号通路诱导HCT116细胞凋亡并阻止细胞侵袭。
