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细胞迁移
流式细胞术
双氢青蒿素
化学
活力测定
干细胞
癌症研究
STAT蛋白
细胞
分子生物学
磷酸化
生物
细胞生物学
生物化学
免疫学
青蒿素
疟疾
恶性疟原虫
作者
Yan Zhang,Liwei Ma,Lili Deng,Zhuang-Miao Zhang
出处
期刊:PubMed
日期:2022-10-01
卷期号:30 (5): 1428-1434
被引量:1
标识
DOI:10.19746/j.cnki.issn.1009-2137.2022.05.019
摘要
To investigate the potential antitumor effect and its mechanism of dihydroartemisinin (DHA) on diffuse large B-cell lymphoma (DLBCL).OCI-Ly7 cells were respectively treated with different concentrations of DHA (0, 12.5, 25, 50 and 100 μmol/L) , CCK-8 was used to detect the cells viability. Subsequently, OCI-Ly7 cells were divided into 5 groups : DHA 0,25,50,100 μmol / L and DHA (100 μmol / L) + Colivelin (STAT3 activator). Aldehyde dehydrogenase (ALDH) positive cells were sorted by flow cytometry, the sphere-forming ability of stem cells was detected. Transwell assay and scratch test were used to analyze the invasion and migration of cells. Western blot was used to detect the expression of migration and invasion-related proteins, as well as the phosphorylation levels of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3(STAT3).DHA induced obvious cytotoxicity to OCI-Ly7 cells. Compared with the control group, the stem cell-like properties, invasion and migration of OCI-Ly7 were significantly inhibited in DHA 50 μmol/L group and 100 μmol/L group, while the phosphorylation levels of JAK2 and STAT3 were significantly reduced. There was no significant difference in DHA 25 μmol/L group compared with the control group. Treated with Colivelin, the inhibition of DHA on OCI-Ly7 stem cell-like properties, invasion and migration was significantly reversed, and the expression of p-STAT3 was significantly up-regulated.DHA has antitumor effect on DLBCL, and its mechanism may be through inhibiting the activation of JAK2/STAT3 pathway to inhibit the stem cell-like properties, invasion and migration of DLBCL cells.二氢青蒿素对弥漫性大B细胞淋巴瘤发挥抗肿瘤作用的研究.探究二氢青蒿素(dihydroartemisinin,DHA)对弥漫性大B细胞淋巴瘤(DLBCL)的潜在抗癌作用及相关机制.用不同浓度的DHA(0、12.5、25、50和100 μmol/L)分别处理DLBCL细胞OCI-Ly7,采用CCK-8检测细胞活力。随后,将OCI-Ly7细胞分为5组:DHA 0、25、50、100 μmol/L和DHA(100 μmol/L)+ Colivelin (STAT3激活剂),流式分选乙醛脱氢酶(ALDH)阳性细胞,检测干细胞成球能力,Transwell实验和划痕实验分析细胞的侵袭和迁移能力,采用Western blot法检测迁移和侵袭相关蛋白的表达及Janus激酶2(JAK2)和信号传导与转录激活因子3(STAT3)的磷酸化水平.DHA对OCI-Ly7细胞具有明显的细胞毒性作用。与对照组比较,DHA 50 μmol/L组和100 μmol/L组OCI-Ly7细胞的干细胞样特性、侵袭和迁移被明显抑制,JAK2和STAT3的磷酸化水平显著降低,DHA25 μmol/L组较对照组无显著性差异;加入Colivelin明显逆转了DHA 对OCI-Ly7细胞的干细胞样特性、侵袭和迁移的抑制,并显著上调p-STAT3蛋白表达.DHA对 DLBCL具有抗肿瘤作用,其机制可能是通过抑制JAK2/STAT3通路激活从而抑制DLBCL细胞的干细胞样特性、侵袭和迁移.
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