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盖帕瓦林通过下调COX2表达抑制骨肉瘤进展。

Geiparvarin Inhibits the Progression of Osteosarcoma by Down-regulating COX2 Expression.

作者信息

Wang Bin, Du Jia, Zhang Zhiming, Huang Ping, Chen Shu, Zou Hua

机构信息

Department of Oncology, Daping Hospital, Army Medical University, Chongqing 400042, China.

Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing, 400016, China.

出版信息

Curr Cancer Drug Targets. 2023;23(5):379-387. doi: 10.2174/1568009623666221208113432.

Abstract

BACKGROUND

Geiparvarin (GN) is a natural compound isolated from the leaves of Geijera parviflora and exhibits anticancer activity. Nevertheless, little is known about its anticancer mechanism and anti-osteosarcoma (OS) effects.

AIM

This study explored whether GN effectively inhibits the growth and metastasis of osteosarcoma (OS) through a series of in vitro and in vivo experiments.

METHODS

Cell proliferation was measured by colony formation and MTT assays, and cell invasion was detected by Transwell assay. Flow cytometry and caspase-3 activity assays were carried out to examine cell apoptosis, and western blot analysis was performed to assess protein expression. In the animal experiments, the changes in relevant indexes were determined by immunohistochemistry and tumor vessel imaging.

RESULTS

Animal experiments showed that GN treatment significantly inhibited the growth and lung metastasis of OS, accompanied by increased apoptosis. In addition, GN treatment notably diminished COX2 expression and angiogenesis in OS. Moreover, COX2 overexpression nullified GN-induced decline in angiogenesis, growth, and lung metastasis and increased apoptosis in OS. Of note, the body weight of mice was enhanced after GN treatment, and the pathological examination manifested that GN treatment did not cause any damage to major organs.

CONCLUSION

Our data indicated that GN might depress the growth, metastasis, and angiogenesis of OS by decreasing COX2 expression, suggesting GN is a favorable candidate drug for OS treatment without side effects. Hence, it can be concluded that geiparvarin inhibits OS progression by reducing COX2 expression.

摘要

背景

格帕瓦林(GN)是一种从小花格木树叶中分离出的天然化合物,具有抗癌活性。然而,其抗癌机制及抗骨肉瘤(OS)作用却鲜为人知。

目的

本研究通过一系列体外和体内实验,探究GN是否能有效抑制骨肉瘤(OS)的生长和转移。

方法

采用集落形成实验和MTT实验检测细胞增殖,通过Transwell实验检测细胞侵袭。进行流式细胞术和半胱天冬酶-3活性实验以检测细胞凋亡,并进行蛋白质印迹分析以评估蛋白质表达。在动物实验中,通过免疫组织化学和肿瘤血管成像确定相关指标的变化。

结果

动物实验表明,GN治疗显著抑制了OS的生长和肺转移,并伴有细胞凋亡增加。此外,GN治疗显著降低了OS中COX2的表达和血管生成。而且,COX2过表达消除了GN诱导的血管生成、生长和肺转移的下降以及OS中细胞凋亡的增加。值得注意的是,GN治疗后小鼠体重增加,病理检查表明GN治疗未对主要器官造成任何损害。

结论

我们的数据表明,GN可能通过降低COX2表达来抑制OS的生长、转移和血管生成,这表明GN是一种无副作用的OS治疗候选药物。因此,可以得出结论,格帕瓦林通过降低COX2表达来抑制OS进展。

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