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β-榄香烯通过调节 lncRNA HULC 介导的凋亡通路抑制弥漫大 B 细胞淋巴瘤的肿瘤生长。

β-Elemene suppresses tumor growth of diffuse large B-cell lymphoma through regulating lncRNA HULC-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, Hangzhou, Zhejiang 310013, PR China.

出版信息

Biosci Rep. 2020 Feb 28;40(2). doi: 10.1042/BSR20190804.

Abstract

BACKGROUND

Diffuse large B-cell lymphoma (DLBCL) is considered the most common aggressive subtype of lymphoma. A number of DLBCL patients fail to achieve a response to currently available therapies or develop resistance. β-Elemene is derived from herb Curcuma wenyujin, and exhibits anti-tumor activity in both solid and non-solid tumors through modulating several molecular signaling pathways. We aimed to explore the role of β-elemene in DLBCL treatment and elucidate the involved mechanism.

MATERIALS AND METHODS

Cell viability, apoptosis and expressions of related proteins were assessed and in vivo study were performed to determine the tumor suppressive effect of β-elemene and explore the molecular mechanisms.

RESULTS

β-Elemene significantly suppressed the viability of DLBCL cells, and β-elemene down-regulated the lncRNA HULC expression and regulated key pro-apoptotic and anti-apoptotic proteins to induce significant apoptosis of DLBCL cells. HULC overexpression could decrease the β-elemene induced apoptosis, while HULC knockdown increased the apoptosis in DLBCL cells. In vivo study further confirmed that β-elemene could suppress the growth of DLBCL xenograft and regulate the HULC expression and the critical proteins of the apoptotic pathway.

CONCLUSION

β-Elemene performs as a tumor suppressor and modulator of HULC-mediated apoptotic pathway in DLBCL and will be an alternative candidate for clinical application.

摘要

背景

弥漫性大 B 细胞淋巴瘤(DLBCL)被认为是最常见的侵袭性淋巴瘤亚型。许多 DLBCL 患者对目前可用的治疗方法没有反应或产生耐药性。β-榄香烯来源于莪术,通过调节多种分子信号通路,在实体瘤和非实体瘤中均具有抗肿瘤活性。我们旨在探讨β-榄香烯在 DLBCL 治疗中的作用,并阐明其相关机制。

材料和方法

评估细胞活力、细胞凋亡和相关蛋白的表达,并进行体内研究,以确定β-榄香烯的肿瘤抑制作用,并探讨其分子机制。

结果

β-榄香烯显著抑制 DLBCL 细胞的活力,β-榄香烯下调 lncRNA HULC 的表达,并调节关键的促凋亡和抗凋亡蛋白,诱导 DLBCL 细胞发生显著凋亡。HULC 的过表达可降低β-榄香烯诱导的细胞凋亡,而 HULC 的敲低则增加了 DLBCL 细胞的凋亡。体内研究进一步证实,β-榄香烯可抑制 DLBCL 异种移植瘤的生长,并调节 HULC 的表达和凋亡途径的关键蛋白。

结论

β-榄香烯在 DLBCL 中作为肿瘤抑制因子和 HULC 介导的凋亡途径的调节剂发挥作用,将成为临床应用的替代候选药物。

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