Icaritin induces lytic cytotoxicity in extranodal NK/T-cell lymphoma.
Icaritin induces lytic cytotoxicity in extranodal NK/T-cell lymphoma.
复制标题
淫羊藿素在结外 NK/T 细胞淋巴瘤中诱导裂解性细胞毒性
DOI：
10.1186/s13046-015-0133-x
复制
发表时间：
2015-02-15
期刊：
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Wu T;Wang S;Wu J;Lin Z;Sui X;Xu X;Shimizu N;Chen B;Wang X
结外NK/ t细胞淋巴瘤（ENKL）是一种与eb病毒（EBV）感染相关的侵袭性血液系统恶性肿瘤。它通常对常规化疗具有耐药性，预后较差。淫羊藿苷（Icaritin）是一种从中草药淫羊藿（Herba Epimedii）中提取的化合物，已被报道对多种癌细胞具有抗肿瘤作用。在本研究中，我们研究了淫羊藿苷对两种ebv阳性ENKL细胞系SNK-10和SNT-8的细胞毒性作用，以及潜在的分子机制。将ENKL细胞株SNK-10和SNT-8暴露于不同浓度的淫羊藿苷中，并观察其作用时间。分析处理后的细胞增殖、细胞周期和细胞凋亡情况。Western blot检测信号通路中Stat3和Akt蛋白磷酸化水平以及ebv编码的LMP1蛋白磷酸化水平。实时荧光定量PCR检测EBV基因的表达。结果表明，淫羊藿苷具有剂量依赖性，可抑制ENKL细胞增殖，诱导G2/M期细胞凋亡和细胞周期阻滞。此外，Icaritin上调Bax，下调Bcl-2和pBad，激活caspase-3和caspase-9。Icaritin的抗增殖和促凋亡作用可能是通过LMP1下调抑制Stat3和Akt通路介导的。重要的是，Icaritin在ENKL细胞中诱导EBV溶解基因表达，并且Icaritin与抗病毒药物更昔洛韦（GCV）合用诱导ENKL细胞凋亡比Icaritin或GCV单用更有效。这些发现表明，ebv靶向方法可能具有显著的ENKL治疗潜力。
Extranodal NK/T-cell lymphoma (ENKL) is an aggressive hematological malignancy associated with Epstein–Barr virus (EBV) infection. It is often resistant to conventional chemotherapy and has a poor prognosis. Icaritin, a compound derived from Chinese herbal medicine, Herba Epimedii, has been reported to exert antitumor effects on a variety of cancer cell lines. In the present study, we investigated the cytotoxic effects of Icaritin on the two EBV-positive ENKL cell lines SNK-10 and SNT-8, along with the underlying molecular mechanisms. ENKL cell lines SNK-10 and SNT-8 were exposed to different concentrations of Icaritin for the indicated time. Treated cells were analyzed for cell proliferation, cell cycle, and cell apoptosis. Phosphorylation of Stat3 and Akt proteins in signaling pathways and the EBV-encoded LMP1 proteins were measured by Western blot. Expression of EBV genes was assessed by Real-Time PCR. Our results showed that Icaritin dose-dependently inhibits ENKL cell proliferation and induces apoptosis and cell cycle arrest at G2/M phase. Additionally, Icaritin upregulates Bax, downregulates Bcl-2 and pBad, and activates caspase-3 and caspase-9. The anti-proliferative and pro-apoptotic effects of Icaritin are likely mediated by inhibition of Stat3 and Akt pathways through LMP1 downregulation. Importantly, Icaritin induces EBV lytic gene expression in ENKL cells, and the combination of Icaritin and the antiviral drug ganciclovir (GCV) is more effective in inducing ENKL cells apoptosis than Icaritin or GCV alone. These findings indicate that EBV-targeted approaches may have significant therapeutic potential for ENKL treatment.
登录
查看更多内容
DOI：
10.1186/1756-9966-33-7
发表时间：
2014-01-17
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Liang L;Nong L;Zhang S;Zhao J;Ti H;Dong Y;Zhang B;Li T
通讯作者：
Li T
影响因子：
3.7
作者：
Hong J;Zhang Z;Lv W;Zhang M;Chen C;Yang S;Li S;Zhang L;Han D;Zhang W
通讯作者：
Zhang W
影响因子：
20.3
作者：
Nagata, H;Konno, A;Shimizu, N
通讯作者：
Shimizu, N
影响因子：
3.3
作者：
Lima, Raquel T.;Seca, Hugo;Helena Vasconcelos, M.
通讯作者：
Helena Vasconcelos, M.
影响因子：
2.2
作者：
Ghosh SK;Perrine SP;Faller DV
通讯作者：
Faller DV