Ginsenoside Rg3 inhibits growth and epithelial-mesenchymal transition of human oral squamous carcinoma cells by down-regulating miR-221 (Retracted article. See vol. 928, 2022)
Ginsenoside Rg3 inhibits growth and epithelial-mesenchymal transition of human oral squamous carcinoma cells by down-regulating miR-221 (Retracted article. See vol. 928, 2022)
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DOI：
10.1016/j.ejphar.2019.03.040
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发表时间：
2019-06-15
影响因子：
5
通讯作者：
Xing, Dayuan
中科院分区：
文献类型：
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作者：
Cheng, Zhou;Xing, Dayuan
人参皂苷Rg3是从人参根部分离出来的，已被发现对多种人类癌症具有抗癌活性。然而，目前还没有关于Rg3对口腔鳞状细胞癌(OSCC)作用的文献报道。本研究探讨了Rg3对口腔鳞癌可能的抗癌作用及其可能的分子机制。采用CCK-8比色法和BrdU比色法分别检测细胞活力和细胞增殖。Annexin V-FITC/PI法检测细胞凋亡。用细胞转染法改变miR-221和TIMP3的表达。采用定量逆转录聚合酶链式反应(QRT-PCR)和免疫印迹法检测细胞凋亡、上皮-间充质转化(EMT)过程、PI3K/AKT信号通路和MAPK/ERK信号通路相关分子的表达。体内建立口腔鳞癌原位小鼠模型，测量肿瘤体积。我们发现Rg3处理抑制了人口腔鳞癌SCC-9和HSC-5细胞的存活、增殖和EMT过程，但促进了细胞的凋亡。MIR-221在口腔鳞癌组织和细胞中高表达。Rg3降低口腔鳞癌细胞miR-221的表达。MiR-221上调可阻断Rg3对SCC-9和HSC-5细胞活力、增殖、凋亡和EMT过程的影响。TIMP3在口腔鳞癌组织和细胞中低表达，是miR-221的直接靶基因。Rg3通过上调TIMP3失活SCC-9细胞中的PI3K/AKT和MAPK/ERK通路。在体内，Rg3可缩小口腔鳞状细胞癌原位小鼠模型的肿瘤体积。结论：Rg3对口腔鳞癌的抗癌作用可能是通过下调miR-221，上调TIMP3，进而失活PI3K/AKT和MAPK/ERK通路实现的。
Ginsenoside Rg3, isolated from the roots of Panax ginseng, has been found to exert anti-cancer activity on multiple human cancers. However, there is no any literature available about the effect of Rg3 on oral squamous cell carcinoma (OSCC). This study investigated the possible anti-cancer effects of Rg3 on OSCC, as well as the possible molecular mechanisms. In vitro, cell viability and proliferation were respectively detected by CCK-8 assay and BrdU assay. Cell apoptosis was detected by Annexin V-FITC/PI assay. Cell transfection was used to change the expression of miR-221 and TIMP3. qRT-PCR and western blotting were performed to measure the expression of molecules involving in cell apoptosis, epithelial-mesenchymal transition (EMT) process, PI3K/AKT pathway and MAPK/ERK pathway. In vivo, OSCC orthotopic murine model was established and tumor volumes were measured. We found that Rg3 treatment inhibited viability, proliferation and EMT process of human OSCC SCC-9 and HSC-5 cells, but promoted cell apoptosis. miR-221 was highly expressed in OSCC tissues and cells. Rg3 reduced the expression of miR-221 in OSCC cells. Up-regulation of miR-221 abrogated the effects of Rg3 on SCC-9 and HSC-5 cell viability, proliferation, apoptosis and EMT process. TIMP3 was lowly expressed in OSCC tissues and cells, which was a direct target gene of miR-221. Rg3 inactivated PI3K/AKT and MAPK/ERK pathways in SCC-9 cells by up-regulating TIMP3. In vivo, Rg3 reduced the tumor volume of OSCC orthotopic murine model. In conclusion, Rg3 exerted anti-cancer effects on OSCC might be via down-regulating miR-221, upregulating TIMP3, and then inactivating PI3K/AKT and MAPK/ERK pathways.