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大黄素抑制黑色素瘤细胞的迁移和侵袭。

Emodin Suppresses the Migration and Invasion of Melanoma Cells.

机构信息

Shanghai Key Laboratory of Clinical Geriatric Medicine, Hua Dong Hospital Affiliated to Fu Dan University.

Department of Plastic and Reconstructive Surgery, Hua Dong Hospital Affiliated to Fu Dan University.

出版信息

Biol Pharm Bull. 2021 Jun 1;44(6):771-779. doi: 10.1248/bpb.b20-00807. Epub 2021 Mar 17.

Abstract

Emodin (1,3,8-trihydroxy-6-methylanthraquinone), as an active ingredient in rhubarb roots and rhizomes, has been reported to possess various pharmacological properties including anti-tumor effects. Recent studies have confirmed that emodin inhibited cell proliferation and induced apoptosis of cancer cells. However, the inhibitory effect of emodin on the migration and invasion of melanoma cells and its underlying mechanism are still unclear. In the study, we observed the impercipient effects of emodin in B16F10 and A375 melanoma cells with strong metastatic abilities, focusing on the functions and mechanisms of migration and invasion of B16F10 and A375 melanoma cells. Cell counting kit-8 (CCK-8), colony formation test and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining tests confirmed that emodin possessed anti-proliferative and pro-apoptotic activities in B16F10 and A375 cells. The inhibitory effects on the migration and invasion of B16F10 and A375 cells were proved by wound healing assay and Transwell methods. Moreover, immunofluorescence assay approved the decrease in protein expression of matrix metalloproteinas (MMP)-2/-9 by emodin, and Western blot analyses revealed that emodin could increase the Bax/Bcl-2 ratio and inhibit the MMP-2/-9 protein expression and Wnt/β-catenin pathway in a dose-depended manner. BML-284, as an agonist of Wnt/β-catenin signaling pathway, reversed the effects of emodin on cell growth, migration and invasion in B16F10 cells. These findings may suggest that emodin treatment can be a promising therapeutic strategy for melanoma with highly metastatic abilities.

摘要

大黄素(1,3,8-三羟基-6-甲基蒽醌)作为大黄根和根茎的一种活性成分,已被报道具有多种药理作用,包括抗肿瘤作用。最近的研究证实,大黄素能抑制癌细胞的增殖并诱导其凋亡。然而,大黄素对黑色素瘤细胞迁移和侵袭的抑制作用及其潜在机制尚不清楚。在本研究中,我们观察了大黄素对具有强转移能力的 B16F10 和 A375 黑色素瘤细胞的不明显作用,重点研究了 B16F10 和 A375 黑色素瘤细胞迁移和侵袭的功能和机制。细胞计数试剂盒-8(CCK-8)、集落形成试验和 Annexin V-荧光素异硫氰酸酯(FITC)/碘化丙啶(PI)染色试验证实,大黄素对 B16F10 和 A375 细胞具有抗增殖和促凋亡活性。划痕愈合试验和 Transwell 方法证明了大黄素对 B16F10 和 A375 细胞迁移和侵袭的抑制作用。此外,免疫荧光试验证实了大黄素降低了基质金属蛋白酶(MMP)-2/-9 的蛋白表达,Western blot 分析表明,大黄素能够以剂量依赖的方式增加 Bax/Bcl-2 比值,抑制 MMP-2/-9 蛋白表达和 Wnt/β-catenin 通路。BML-284 作为 Wnt/β-catenin 信号通路的激动剂,逆转了大黄素对 B16F10 细胞生长、迁移和侵袭的作用。这些发现可能表明,大黄素治疗可能是一种有前途的治疗高转移能力黑色素瘤的策略。

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