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吉非替尼可导致人软骨肉瘤细胞生长停滞并抑制其转移。

Gefitinib causes growth arrest and inhibition of metastasis in human chondrosarcoma cells.

作者信息

Song Jian, Zhu Jiaxue, Zhao Qiang, Tian Baofang

机构信息

Department of Orthopaedics, Shandong Jining No.1 People's Hospital, 6 Jiankang Road, Jining, Shandong, 272000, China.

出版信息

J BUON. 2015 May-Jun;20(3):894-901.

Abstract

PURPOSE

Chondrosarcomas are primary malignant cartilage-forming tumors of bone which are not responsive either to chemotherapy or radiation treatment and display potent capacity to invade locally and cause distant metastasis. Epidermal growth factor receptor (EGFR) pathway plays an important role in the development and progression of many cancers. However, the effect of EGFR inhibitor gefitinib on cell growth and metastasis in human chondrosarcoma cells is largely unknown.

METHODS

Features of the protein expression of EGFR in 3 human chondrosarcoma cell lines JJ2012, SW1353 and OUMS27 were analyzed. The inhibitory effects of EGFR inhibitor gefitinib on cell proliferation, cell cycle and metastasis were assessed by using MTS, flow cytometry and migration assays, respectively. The expression of metastasis-related proteins was evaluated by western blotting.

RESULTS

All the three human chondrosarcoma cell lines expressed EGFR protein. Gefitinib significantly inhibited the growth, induced cell cycle arrest and decreased the migra- tion ability of human chondrosarcoma cells. In addition, gefitinib also reduced the expression of metastasis-related proteins, basic fibroblast growth factor (bFGF), matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9).

CONCLUSIONS

The discovery that gefitinib inhibited the proliferation and reduced the metastatic capacity of chondrosarcoma cells may help increase the understanding of the mechanism underlying human chondrosarcoma growth and metastasis. Thus, gefitinib may represent a promising agent for controlling chondrosarcoma proliferation and metastasis.

摘要

目的

软骨肉瘤是原发性骨恶性软骨形成肿瘤,对化疗和放疗均无反应,具有强大的局部侵袭和远处转移能力。表皮生长因子受体(EGFR)通路在许多癌症的发生和发展中起重要作用。然而,EGFR抑制剂吉非替尼对人软骨肉瘤细胞生长和转移的影响尚不清楚。

方法

分析3种人软骨肉瘤细胞系JJ2012、SW1353和OUMS27中EGFR的蛋白表达特征。分别采用MTS法、流式细胞术和迁移实验评估EGFR抑制剂吉非替尼对细胞增殖、细胞周期和转移的抑制作用。通过蛋白质印迹法评估转移相关蛋白的表达。

结果

所有3种人软骨肉瘤细胞系均表达EGFR蛋白。吉非替尼显著抑制人软骨肉瘤细胞的生长,诱导细胞周期停滞,并降低其迁移能力。此外,吉非替尼还降低了转移相关蛋白碱性成纤维细胞生长因子(bFGF)、基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-9(MMP-9)的表达。

结论

吉非替尼抑制软骨肉瘤细胞增殖并降低其转移能力这一发现,可能有助于加深对人软骨肉瘤生长和转移机制的理解。因此,吉非替尼可能是控制软骨肉瘤增殖和转移的一种有前景的药物。

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