Polydatin inhibits hepatocellular carcinoma via the AKT/STAT3-FOXO1 signaling pathway
Polydatin inhibits hepatocellular carcinoma via the AKT/STAT3-FOXO1 signaling pathway
复制标题
虎杖甙通过 AKT/STAT3-FOXO1 信号通路抑制肝细胞癌。
DOI：
10.3892/ol.2019.10123
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发表时间：
2019-05-01
期刊：
影响因子：
2.9
通讯作者：
Yang, Xiuhua
中科院分区：
文献类型：
--
作者：
Jiang, Jian;Chen, Yaodong;Yang, Xiuhua
虎杖苷是从虎杖中提取的，具有抗血小板聚集和抗炎作用。然而，虎杖苷与癌症相关性的研究有限，特别是关于上皮-间质转化（EMT）相关的癌细胞迁移和侵袭。本研究的目的是揭示虎杖苷对肝癌细胞的潜在抗癌作用，特别是对EMT的影响。MTT法测定细胞活力。通过伤口愈合和transwell试验评估迁移和侵袭。集落形成率测定检测细胞增殖情况。流式细胞术分析细胞凋亡和细胞周期进程进行后，分别用膜联蛋白V-异硫氰酸荧光素（FITC）/碘化丙啶（PI）和PI单独染色的细胞。采用Western blotting方法研究相关的分子机制。结果表明，虎杖苷通过G（2）/M期阻滞抑制肝癌细胞增殖，抑制肝癌细胞的迁移和侵袭，促进肝癌细胞凋亡。此外，磷酸化（p）-蛋白激酶B（AKT），p-Janus激酶1和p-信号转导和转录激活因子3（STAT 3）的水平随着虎杖苷浓度的增加而降低，叉头盒蛋白O 1（FOXO 1）的表达上调。此外，EMT的各种标志物的表达水平被逆转后用虎杖苷处理。因此，本研究证实虎杖苷可能通过G（2）/M阻滞抑制肝癌细胞增殖，并抑制EMT相关的迁移和侵袭。虎杖苷可能通过阻断AKT/STAT 3-FOXO 1信号通路促进肝癌细胞凋亡。
Polydatin, extracted from Polygonum cuspidatum, is known for its anti-platelet aggregation and anti-inflammatory effects. However, studies on the association of polydatin with cancer are limited, particularly with regards to epithelial-mesenchymal transition (EMT)-associated migration and invasion of cancer cells. The purpose of the present study was to reveal the potential anticancer effects of polydatin on hepatocellular carcinoma (HCC) cells, particularly its effects on EMT. MTT assay was used to determine cell viability. Migration and invasion were evaluated through wound healing and transwell assays. Colony formation efficiency assay was conducted to detect proliferation. Flow cytometric analyses of apoptosis and cell cycle progression were performed following cells staining with Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) and PI alone, respectively. Western blotting was used to investigate relevant molecular mechanisms. The results indicated that polydatin inhibited proliferation via G(2)/M arrest, suppressed migration and invasion of HCC cells, and promoted their apoptosis. In addition, phosphorylated (p)-protein kinase B (AKT), p-Janus kinase 1 and p-signal transducer and activator of transcription 3 (STAT3) levels were decreased as polydatin concentrations increased, and forkhead box protein O1 (FOXO1) expression was upregulated. Furthermore, the expression levels of various markers of EMT were reversed following treatment with polydatin. In conclusion, the present study validated that polydatin may inhibit proliferation via G(2)/M arrest, and suppressed EMT-associated migration and invasion of HCC cells. The results also suggested that polydatin may promote HCC cell apoptosis by blocking the AKT/STAT3-FOXO1 signaling pathway.