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脂肪甘油单酯酶抑制剂抑制宫颈癌的增殖、迁移、侵袭、肿瘤生长并诱导细胞凋亡。

Inhibition of monoacylglycerol lipase restrains proliferation, migration, invasion, tumor growth and induces apoptosis in cervical cancer.

机构信息

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

Department of Gynecology and Oncology, Jiangxi Cancer Hospital, Nanchang, Jiangxi, China.

出版信息

J Obstet Gynaecol Res. 2022 Feb;48(2):456-466. doi: 10.1111/jog.15110. Epub 2021 Dec 7.

Abstract

AIM

Cervical cancer is one of common diseases among women. There are limited therapies for patients with metastatic or recurrent cervical cancer. This study sought to explore the role of monoacylglycerol lipase (MAGL), an important metabolic enzyme, in cervical cancer progression.

METHODS

In in vitro experiments, MAGL expression was inhibited by si-MAGL or JZL184 in cervical cancer cells. Quantitative real-time polymerase chain reaction and western blotting were performed to measure the expression of target molecules. Proliferation of cervical cancer cells was assessed by CCK-8 and colony formation assays. Apoptosis and cell cycle progression were evaluated by flow cytometry. The migration and invasion were detected by transwell assay. The in vivo tumor growth was detected in nude mice. TUNEL was utilized to observe apoptotic cells in tumor tissues.

RESULTS

MAGL was upregulated in cervical cancer tissues and cells. Further, MAGL inhibition suppressed the growth of cervical cancer cells in vitro and in vivo. In addition, apoptosis and G1-phase cell cycle arrest were induced by MAGL knockdown. MAGL silencing-mediated upregulation of Bax and cleaved caspase-3, and downregulation of Bcl-2 was responsible for triggering apoptosis. More importantly, the migration and invasion of cervical cancer cells were restrained by MAGL depletion.

CONCLUSIONS

MAGL drives the progression of cervical cancer, which can be a promising candidate to identify effective therapy for cervical cancer.

摘要

目的

宫颈癌是女性常见疾病之一。对于转移性或复发性宫颈癌患者,治疗方法有限。本研究旨在探讨单酰基甘油脂肪酶(MAGL)作为一种重要的代谢酶在宫颈癌进展中的作用。

方法

在体外实验中,通过 si-MAGL 或 JZL184 抑制宫颈癌细胞中 MAGL 的表达。采用定量实时聚合酶链反应和蛋白质印迹法检测靶分子的表达。通过 CCK-8 和集落形成实验评估宫颈癌细胞的增殖。通过流式细胞术评估细胞凋亡和细胞周期进程。通过 Transwell 测定检测细胞迁移和侵袭。在裸鼠中检测体内肿瘤生长。利用 TUNEL 观察肿瘤组织中的凋亡细胞。

结果

MAGL 在宫颈癌组织和细胞中上调。此外,MAGL 抑制可抑制宫颈癌细胞在体外和体内的生长。此外,MAGL 敲低可诱导细胞凋亡和 G1 期细胞周期阻滞。MAGL 沉默介导的 Bax 和 cleaved caspase-3 上调以及 Bcl-2 下调负责触发细胞凋亡。更重要的是,MAGL 耗竭可抑制宫颈癌细胞的迁移和侵袭。

结论

MAGL 驱动宫颈癌的进展,可能成为识别宫颈癌有效治疗方法的有前途的候选物。

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