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冬凌草甲素通过抑制基质金属蛋白酶表达和STAT3信号通路来抑制人骨肉瘤细胞的增殖、迁移和侵袭。

Oridonin inhibits the proliferation, migration and invasion of human osteosarcoma cells via suppression of matrix metalloproteinase expression and STAT3 signalling pathway.

作者信息

Du Yiqun, Zhang Jian, Yan Shiyan, Tao Zhonghua, Wang Chenchen, Huang Mingzhu, Zhang Xiaowei

机构信息

Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

出版信息

J BUON. 2019 May-Jun;24(3):1175-1180.

Abstract

PURPOSE

Oridonin, a diterpenoid, has been reported to exhibit anticancer activity against a wide range of cancer types.In this study, the effect Oridonin was examined against human osteosarcoma cells.

METHODS

The human osteosarcoma cells U2OS were treated with various concentrations of Oridonin from 0-200 μM for 24 h. The anti-proliferative effects of Oridonin were measured by cell viability assay. DAPI and annexin V/propidium iodide (PI) assays were employed to examine the induction of apoptosis. Transwell assay was performed to examine the cell migration and invasion. Expression analysis was performed by western blot.

RESULTS

Oridonin inhibited the proliferation of U2OScells and exhibited an IC50 of 30 µM. The antiproliferative effects were mainly found to be due to induction of apoptosis as indicated by DAPI staining. Moreover, the annexin V/PI staining showed that the percentage of the apoptotic cells increased with increase in the concentration of Oridonin. The induction of apoptosis was also related with upregulation of Bax, Caspase 3 and 9 expression and downregulation of Bcl-2. Oridonin was also found to cause significant decrease in the expression of MMP-2, 3 and 9 concentration-dependently. Transwell assay showed that Oridonin inhibited the migration and invasion of the U2OS cells.

CONCLUSION

It is concluded that Oridonin exhibits significant antiproliferative effects on the osteosarcoma cells and may prove essential in the development of systemic therapy for osteosarcoma.

摘要

目的

冬凌草甲素,一种二萜类化合物,已被报道对多种癌症类型具有抗癌活性。在本研究中,检测了冬凌草甲素对人骨肉瘤细胞的作用。

方法

用0 - 200μM的不同浓度冬凌草甲素处理人骨肉瘤细胞U2OS 24小时。通过细胞活力测定来检测冬凌草甲素的抗增殖作用。采用DAPI和膜联蛋白V/碘化丙啶(PI)检测来检测细胞凋亡的诱导情况。进行Transwell检测以检测细胞迁移和侵袭。通过蛋白质印迹法进行表达分析。

结果

冬凌草甲素抑制U2OS细胞的增殖,IC50为30μM。如DAPI染色所示,抗增殖作用主要是由于诱导细胞凋亡。此外,膜联蛋白V/PI染色表明,凋亡细胞的百分比随着冬凌草甲素浓度的增加而增加。细胞凋亡的诱导还与Bax、半胱天冬酶3和9的表达上调以及Bcl-2的表达下调有关。还发现冬凌草甲素能浓度依赖性地显著降低MMP-2、3和9的表达。Transwell检测表明,冬凌草甲素抑制U2OS细胞的迁移和侵袭。

结论

得出结论,冬凌草甲素对骨肉瘤细胞具有显著的抗增殖作用,可能在骨肉瘤全身治疗的发展中至关重要。

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