Musculoskeletal Tumor Center, Peking University People's Hospital, No. 11 Xizhimen South Street, 100044, Beijing, China.
J Cancer Res Clin Oncol. 2010 Aug;136(8):1179-85. doi: 10.1007/s00432-010-0765-3. Epub 2010 Feb 2.
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.
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.
EGCG effectively inhibited cellular proliferation and induced apoptosis of SW1353 and CRL-7891. EGCG inhibited the human Indian Hedgehog pathway, down-regulated 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.
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.
软骨肉瘤是一种预后不良的软组织肉瘤，对常规化疗无反应。软骨肉瘤细胞快速增殖的调节机制以及这种肉瘤的特殊侵袭性仍知之甚少。在这项研究中，我们研究了表没食子儿茶素没食子酸酯（EGCG）对软骨肉瘤细胞生长和凋亡的影响。
用 EGCG 培养软骨肉瘤细胞系 SW1353 和 CRL-7891，并进行 MTT 检测以测试 EGCG 的细胞毒性。流式细胞术和 DAPI 染色用于观察 EGCG 引起的细胞凋亡。为了探讨 EGCG 对印度刺猬信号通路和凋亡相关蛋白的影响，我们使用 RT-PCR 和 Western blot 检测了印度刺猬信号通路中 PTCH 和 Gli-1 的表达。同时，通过 Western blot 分析评估了 Bcl-2、Bax 和 caspase-3 的表达。
EGCG 有效抑制了 SW1353 和 CRL-7891 的细胞增殖并诱导其凋亡。EGCG 抑制了人印度刺猬通路，下调了 PTCH 和 Gli-1 水平，并通过 DAPI 染色后流式细胞术证实诱导了凋亡。软骨肉瘤细胞中 EGCG 处理后 caspase-3 的蛋白表达水平没有变化；然而，Bcl-2 的表达水平明显降低，Bax 的表达水平明显升高。
我们的研究结果表明，EGCG 对软骨肉瘤细胞系的体外生长抑制有效，并提示 EGCG 可能是软骨肉瘤患者的一种新的治疗选择。
