(-)-Epigallocatechin-3-gallate induces apoptosis and suppresses proliferation by inhibiting the human Indian Hedgehog pathway in human chondrosarcoma cells

被引:40
|
作者
Tang, Guo-Qing [1 ]
Yan, Tai-Qiang [1 ]
Guo, Wei [1 ]
Ren, Ting-Ting [1 ]
Peng, Chang-Liang [1 ]
Zhao, Hui [1 ]
Lu, Xin-Chang [1 ]
Zhao, Fu-Long [1 ]
Han, Xiaoguang [2 ]
机构
[1] Peking Univ, Peoples Hosp, Musculoskeletal Tumor Ctr, Beijing 100044, Peoples R China
[2] Peking Univ, Hosp 3, Dept Orthopaed, Beijing 100044, Peoples R China
关键词
Chondrosarcoma; EGCG; Indian Hedgehog pathway; Apoptosis; SIGNAL-TRANSDUCTION; GREEN TEA; NETWORK; FAMILY;
D O I
10.1007/s00432-010-0765-3
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose Chondrosarcoma is a soft tissue sarcoma with a poor prognosis that is unresponsive to conventional chemotherapy. The regulatory mechanisms for the rapid proliferation of chondrosarcoma cells and the particular aggressiveness of this sarcoma remain poorly understood. In this study, we investigate the effect of epigallocatechin-3-gallate (EGCG) on growth and apoptosis of chondrosarcoma cells. Methods The chondrosarcoma cell lines, SW1353 and CRL-7891, were cultured with and without EGCG. The MTT assay was used to test the cytotoxicity of EGCG. Flow cytometry and DAPI staining were used to observe cell apoptosis caused by EGCG. To explore the effect of EGCG on the Indian Hedgehog signaling pathway and apoptosis-related proteins, RT-PCR and Western blotting were used to detect the expression of PTCH and Gli-1 in the Indian Hedgehog signaling pathway. Meanwhile, expression of Bcl-2, Bax, and caspase-3 were also evaluated by Western blot analysis. Results EGCG effectively inhibited cellular proliferation and induced apoptosis of SW1353 and CRL-7891. EGCG inhibited the human Indian Hedgehog pathway, downregulated PTCH and Gli-1 levels, and induced apoptosis as confirmed by DAPI staining followed by flow cytometry. Protein expression levels of caspase-3 were unchanged in response to EGCG treatment in chondrosarcoma cells; however, the expression levels of Bcl-2 were significantly decreased and the levels of Bax were significantly increased. Conclusions Our findings demonstrate that EGCG is effective for growth inhibition of a chondrosarcoma cell lines in vitro, and suggest that EGCG may be a new therapeutic option for patients with chondrosarcoma.
引用
收藏
页码:1179 / 1185
页数:7
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