Zhang Chun, Cui Guo-hui, Liu Fang, Wu Qiu-ling, Chen Yan
Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Acta Pharmacol Sin. 2006 Nov;27(11):1438-46. doi: 10.1111/j.1745-7254.2006.00415.x.
To investigate the antiproliferative effect of triptolide on B-NHL cell line Raji cells, to study its effect on lymph node metastasis in patients with non-Hodgkin's lymphoma (NHL) in vitro, and to explore the underlying mechanism regulating SDF-1/CXCR4 axis.
The effects of triptolide on the growth of Raji cells were studied by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium (MTT) assay. The effects of triptolide on SDF-1 mRNA expression in lymph node stromal cells from patients with NHL were determined by reverse transcriptase-polymerase chain reaction (RT-PCR). The effects of triptolide on CXCR4 expression on lymphoma cells freshly isolated from the lymph nodes of these patients were studied by flow cytometric analysis. Chemotaxis assays were performed to observe the effects of triptolide on migration of primary lymphoma cells towards recombinant human SDF-1 alpha (rhSDF-1 alpha) or cultured lymph node stromal cells in vitro.
Triptolide inhibited the proliferation of B-NHL cell line Raji cells in a dose- and time-dependent manner with a 24-h IC50 value of 43.06 nmol/L and a 36-h IC50 value of 25.08 nmol/L. The expression of SDF-1alpha mRNA in lymph node stromal cells obtained from patients with NHL was decreased after treatment by triptolide at concentrations of 25 and 50 nmol/L for 24 h. Flow cytometry analysis showed that the CXCR4 expression on primary lymphoma cells were downregulated gradually in a dose-dependent manner following triptolide treatment. Chemotaxis assays revealed that the migration of freshly isolated lymphoma cells towards either rhSDF-1 or cultured lymph node stromal cells was markedly inhibited by the addition of triptolide in vitro, and the inhibition was dose-dependent.
Triptolide can inhibit the proliferation of B-NHL cell line Raji cells. Moreover, triptolide is able to inhibit the migration of lymphoma cells via lymph nodes in vitro. The potential antitumor mechanisms of triptolide are related to the antiproliferative effect and the blockage of SDF-1/CXCR4 axis.
研究雷公藤甲素对B-NHL细胞系Raji细胞的抗增殖作用，探讨其体外对非霍奇金淋巴瘤（NHL）患者淋巴结转移的影响，并探究调控SDF-1/CXCR4轴的潜在机制。
采用3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2H-四氮唑溴盐（MTT）法研究雷公藤甲素对Raji细胞生长的影响。通过逆转录聚合酶链反应（RT-PCR）检测雷公藤甲素对NHL患者淋巴结基质细胞中SDF-1 mRNA表达的影响。采用流式细胞术分析雷公藤甲素对这些患者淋巴结中新鲜分离的淋巴瘤细胞上CXCR4表达的影响。进行趋化实验以观察雷公藤甲素对原代淋巴瘤细胞向重组人SDF-1α（rhSDF-1α）或体外培养的淋巴结基质细胞迁移的影响。
雷公藤甲素以剂量和时间依赖性方式抑制B-NHL细胞系Raji细胞的增殖，24小时IC50值为43.06 nmol/L，36小时IC50值为25.08 nmol/L。用浓度为25和50 nmol/L的雷公藤甲素处理24小时后，NHL患者获得的淋巴结基质细胞中SDF-1α mRNA的表达降低。流式细胞术分析表明，雷公藤甲素处理后，原代淋巴瘤细胞上的CXCR4表达呈剂量依赖性逐渐下调。趋化实验显示，在体外添加雷公藤甲素可显著抑制新鲜分离的淋巴瘤细胞向rhSDF-1或培养的淋巴结基质细胞的迁移，且抑制作用呈剂量依赖性。
雷公藤甲素可抑制B-NHL细胞系Raji细胞的增殖。此外，雷公藤甲素能够在体外抑制淋巴瘤细胞通过淋巴结的迁移。雷公藤甲素潜在的抗肿瘤机制与抗增殖作用及阻断SDF-1/CXCR4轴有关。
