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小白菊内酯诱导 Epstein-Barr 病毒阳性伯基特淋巴瘤细胞凋亡和溶解细胞毒性。

Parthenolide induces apoptosis and lytic cytotoxicity in Epstein-Barr virus-positive Burkitt lymphoma.

机构信息

Department of Hematology, Zhongshan Hospital, Xiamen University, Xiamen 361004, PR China.

出版信息

Mol Med Rep. 2012 Sep;6(3):477-82. doi: 10.3892/mmr.2012.959. Epub 2012 Jun 20.

Abstract

Burkitt lymphoma (BL) has been reported to be strongly associated with Epstein-Barr virus (EBV) infection. The fact that EBV is generally present in cancer cells but rarely found in healthy cells represents an opportunity for targeted cancer therapy. One approach is to activate the lytic replication cycle of the latent EBV. Nuclear factor (NF)-κB is thought to play an essential role in EBV lytic infection. Elevated NF-κB levels inhibit EBV lytic replication. Parthenolide (PN) is a sesquiterpene lactone found in medicinal plants, particularly in feverfew (Tanacetum parthenium). The aim of the present study was to analyze the effect of PN on the survival of Raji EBV-positive lymphoma cells. Raji cells were treated with 0, 4 or 6 µmol/l PN for 48 h. MTT assay and western blot analysis were performed to evaluate the findings. Results showd that PN suppressed the growth of the EBV-positive BL cell line, Raji, and activated the transcription of BZLF1 and BRLF1 by inhibiting NF-κB activity. Most notably, when PN was used in combination with ganciclovir (GCV), the cytotoxic effect of PN was amplified. These data suggest that the induction of lytic EBV infection with PN in combination with GCV may be a viral‑targeted therapy for EBV-associated BL.

摘要

伯基特淋巴瘤(BL)与 Epstein-Barr 病毒(EBV)感染密切相关。EBV 通常存在于癌细胞中,而在健康细胞中很少发现,这为靶向癌症治疗提供了机会。一种方法是激活潜伏 EBV 的裂解复制周期。核因子(NF)-κB 被认为在 EBV 裂解感染中发挥重要作用。升高的 NF-κB 水平抑制 EBV 裂解复制。小白菊内酯(PN)是一种倍半萜内酯,存在于药用植物中,尤其是在小白菊(Tanacetum parthenium)中。本研究旨在分析 PN 对 Raji EBV 阳性淋巴瘤细胞存活的影响。Raji 细胞用 0、4 或 6 μmol/L PN 处理 48 h。通过 MTT 测定和 Western blot 分析评估结果。结果表明,PN 抑制 EBV 阳性 BL 细胞系 Raji 的生长,并通过抑制 NF-κB 活性激活 BZLF1 和 BRLF1 的转录。值得注意的是,当 PN 与更昔洛韦(GCV)联合使用时,PN 的细胞毒性作用被放大。这些数据表明,PN 联合 GCV 诱导 EBV 裂解感染可能是 EBV 相关 BL 的病毒靶向治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b26/3493062/a73f827cf3e3/MMR-06-03-0477-g00.jpg

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