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β-榄香烯通过激活 PUMA 介导的凋亡通路对抗伯基特淋巴瘤。

β-elemene against Burkitt's lymphoma via activation of PUMA mediated apoptotic pathway.

机构信息

Department of Hematology, Zhejiang Provincial Hospital of TCM, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, PR China.

Department of Hematology, Zhejiang Hospital, No.12 Lingyin Road, Hangzhou, Zhejiang, 310013, PR China.

出版信息

Biomed Pharmacother. 2018 Oct;106:1557-1562. doi: 10.1016/j.biopha.2018.07.124. Epub 2018 Jul 26.

Abstract

Burkitt's lymphoma is a type of highly aggressive Non-Hodgkin's lymphoma. Although advanced Burkitt's lymphoma is responsive to high-intensity chemotherapy regimens, increasing systemic toxicity, tumor recurrence and metastasis significantly reduce the patient survival. Thus, it is important to investigate novel antitumor agents with safety and effectiveness. β-elemene shows anti-proliferative effect on cancer cells by triggering apoptosis through regulating several molecular signaling pathways. However, its role in the suppression of Burkitt's lymphoma has not yet been fully elucidated. The inhibitory effect of β-elemene in Burkitt's lymphoma was studied in vitro and in vivo, as well as the involved molecular mechanism. The results demonstrated that β-elemene effectively inhibited the growth and induced the apoptosis of Burkitt's lymphoma cells through upregulation of PUMA expression and modulating PUMA related apoptotic signaling pathway. The in vivo data confirmed the anti-tumor effect of β-elemene in the xenografts, suggesting that β-elemene is associated with PUMA activation, leading to Bax and caspase induction and onset of mitochondrial apoptosis.

摘要

伯基特淋巴瘤是一种高度侵袭性的非霍奇金淋巴瘤。尽管晚期伯基特淋巴瘤对高强度化疗方案有反应,但全身性毒性增加、肿瘤复发和转移显著降低了患者的生存率。因此,寻找安全有效的新型抗肿瘤药物非常重要。β-榄香烯通过调节多条分子信号通路触发细胞凋亡对癌细胞具有抗增殖作用。然而,其在伯基特淋巴瘤中的抑制作用尚未完全阐明。本研究在体外和体内研究了β-榄香烯对伯基特淋巴瘤的抑制作用及其相关的分子机制。结果表明,β-榄香烯通过上调 PUMA 表达和调节 PUMA 相关的凋亡信号通路,有效抑制伯基特淋巴瘤细胞的生长并诱导其凋亡。体内数据证实了β-榄香烯在异种移植瘤中的抗肿瘤作用,提示β-榄香烯与 PUMA 的激活有关,导致 Bax 和 caspase 的诱导以及线粒体凋亡的发生。

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