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脂质介质脂氧素A4及其类似物BML-111在黑色素瘤中发挥抗肿瘤作用。

Lipid mediator lipoxin A4 and its analog BML-111 exert antitumor effects in melanoma.

作者信息

Du Yu, Yang Jianing, Su Tangfeng, Shen Zhu, Li Juan

机构信息

Department of Anesthesiology, Sichuan Provincial People's Hospital, University of Electronic and Technology of China, Chengdu, China.

Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China.

出版信息

Ann Transl Med. 2021 May;9(9):802. doi: 10.21037/atm-21-1873.

Abstract

BACKGROUND

LipoxinA4 (LXA4) is an anti-inflammatory lipid mediator which was recently proposed to have antitumor potential. However, the therapeutic effect of LXA4 in melanoma is still unclear. This work aimed to investigate the function of LXA4 and its analog in melanoma invasion through and experiments.

METHODS

The expression of the LXA4 receptor (ALXR) was detected in melanoma tissues and A375 human melanoma cells, using benign melanocytic nevi tissues and human melanocytes as negative controls, respectively. The invasive and apoptotic abilities of A375 cells in the presence or absence of LXA4 were examined by cell invasion assay and flow cytometric analysis. Finally, mice melanoma models were established, and the antitumor effects of BML-111 [5(S), 6(R)-7-trihydroxymethyl heptanoate], an agonist of ALXR, were examined .

RESULTS

ALXR was abundantly expressed in human melanoma tissues. The ALXR messenger RNA (mRNA) and protein expression levels were higher in A375 melanoma cells than in the controls (P<0.05). LXA4 could significantly attenuate the invasion ability of A375 cells (P<0.05). This trend was further enhanced by BML-111, which tended to control the tumor development in A375 melanoma models.

CONCLUSIONS

LXA4 and its analog BML-111 exert antitumor effects and , and may be potential therapeutic options for patients with invasive melanoma.

摘要

背景

脂氧素A4(LXA4)是一种抗炎脂质介质,最近有人提出它具有抗肿瘤潜力。然而,LXA4在黑色素瘤中的治疗效果仍不清楚。这项工作旨在通过[具体实验名称1]和[具体实验名称2]实验研究LXA4及其类似物在黑色素瘤侵袭中的作用。

方法

分别以良性黑素细胞痣组织和人黑素细胞作为阴性对照,检测黑色素瘤组织和A375人黑色素瘤细胞中LXA4受体(ALXR)的表达。通过细胞侵袭实验和流式细胞术分析,检测有无LXA4时A375细胞的侵袭和凋亡能力。最后,建立小鼠黑色素瘤模型,检测ALXR激动剂BML-111[5(S),6(R)-7-三羟甲基庚酸酯]的抗肿瘤作用。

结果

ALXR在人黑色素瘤组织中大量表达。A375黑色素瘤细胞中ALXR信使核糖核酸(mRNA)和蛋白表达水平高于对照组(P<0.05)。LXA4可显著减弱A375细胞的侵袭能力(P<0.05)。BML-111进一步增强了这一趋势,它倾向于控制A375黑色素瘤模型中的肿瘤发展。

结论

LXA4及其类似物BML-111发挥抗肿瘤作用[具体作用机制1]和[具体作用机制2],可能是侵袭性黑色素瘤患者的潜在治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3664/8246158/459c7eccd3f7/atm-09-09-802-f1.jpg

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