EGCG inhibits growth and induces apoptosis in renal cell carcinoma through TFPI-2 overexpression
EGCG inhibits growth and induces apoptosis in renal cell carcinoma through TFPI-2 overexpression
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DOI：
10.3892/or_00000266
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发表时间：
2009-03-01
期刊：
影响因子：
4.2
通讯作者：
Fang, Zujun
中科院分区：
文献类型：
--
作者：
Gu, Bin;Ding, Qiang;Fang, Zujun
表没食子儿茶素没食子酸酯（epigallocatechin gallate）是绿色茶中的主要儿茶素，已被证明可抑制许多肿瘤的增殖并诱导凋亡。表没食子儿茶素没食子酸酯（EGCG）可抑制DNA甲基转移酶（DNMT）活性，引起CpG去甲基化和甲基化沉默基因的重新激活。组织因子途径抑制物-2（TFPI-2）是Kunitz型丝氨酸蛋白酶抑制物家族的成员，与恶性程度的增加呈负相关。我们前期的研究表明TFPI-2的表达与肾癌的侵袭性呈负相关。TFPI-2过表达可诱导肾癌细胞凋亡。TFPI-2在肾癌中的低表达可能与其基因启动子区的甲基化有关。本研究采用MTT法和流式细胞仪检测方法，证实了EGCG对肾癌细胞株786-0的生长有抑制作用，并能诱导其凋亡。Western blotting和real-time RT-PCR结果显示，EGCG可上调TFPI-2的表达。在EGCG处理前后，实时甲基化特异性PCR不能检测到TFPI-2基因启动子在786-0细胞中的甲基化状态。体内侵袭和转移试验表明对照组和治疗组之间没有任何显著差异。我们的研究结果表明，表没食子儿茶素没食子酸酯通过TFPI-2过表达抑制肾细胞癌的生长和诱导凋亡。这是第一个报告表明，表没食子儿茶素没食子酸酯可能是一个有效的药物治疗肾细胞癌。
EGCG (epigallocatechin gallate), the major catechin found in green tea, has been shown to inhibit proliferation and induce apoptosis in many tumors. EGCG can inhibit DNMT (DNA methyltransferase) activity, and cause CpG demethylation and reactivation of methylation-silenced genes. Tissue factor pathway inhibitor-2 (TFPI-2), a member of the Kunitz-type serine proteinase inhibitor family, is inversely related to an increasing degree of malignancy. Our previous study showed that the expression of TFPI-2 and invasiveness of renal cell carcinoma had a negative correlation. Overexpression of TFPI-2 may induce tumor cell apoptosis in renal cell carcinoma. Lower expression of TFPI-2 in renal cell carcinoma was partly due to hypermethylation of the gene promoter. Herein, using MTT and flow cytometry, we demonstrated that EGCG can inhibit growth and induces apoptosis in renal cell carcinoma cell line 786-0. In addition, Western blotting and real-time RT-PCR showed that EGCG can upregulate expression of TFPI-2. Before and after EGCG treatment, real-time methylation specific PCR could not detect methylation status of TFPI-2 gene promoter in cell line 786-0. In vivo invasiveness and metastasis test did not indicate any significant differences between control and treatment group. Our results suggest that EGCG inhibits growth and induces apoptosis in renal cell carcinoma through TFPI-2 overexpression. This is the first report showing that EGCG is likely to be an effective agent for renal cell carcinoma.