Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
Int J Oncol. 2011 May;38(5):1403-8. doi: 10.3892/ijo.2011.951. Epub 2011 Feb 22.
The polyphenol (-)-epigallocatechin-3-gallate (EGCG) is a green tea constituent, which has been shown to inhibit cancer cell growth in vitro, in vivo and in epidemiological studies. In this study, we investigated its effects in gastric cancer cell lines. Five gastric cancer cell lines, the MKN-1, MKN-28, MKN-45, NUGC-3 and TMK-1, were found to be sensitive to EGCG treatment. Of all the cell lines tested, NUGC-3 was the most sensitive. EGCG treatment of NUGC-3 cells induced apoptosis, which was confirmed by sub-G1 analysis, caspase-Glo assay and Western blotting against cleaved PARP and cleaved caspase-3. EGCG treatment lowered survivin and increased Bax and TRAIL expression. Furthermore, EGCG induced p73 activation in NUGC-3 cells. Small interfering RNA against p73 diminished EGCG effects on survivin expression and cell viability. These results show that EGCG induces cell death in gastric cancer cells by apoptosis via inhibition of survivin expression downstream of p73. This study provides a novel mechanism whereby EGCG potentially inhibits cancer cell growth, concluding that EGCG may be a potential candidate in anti-survivin cancer therapy.
多酚（-）-表没食子儿茶素-3-没食子酸酯（EGCG）是绿茶的一种成分，已被证明可在体外、体内和流行病学研究中抑制癌细胞生长。在这项研究中，我们研究了它在胃癌细胞系中的作用。发现五种胃癌细胞系，即 MKN-1、MKN-28、MKN-45、NUGC-3 和 TMK-1，对 EGCG 治疗敏感。在所有测试的细胞系中，NUGC-3 最为敏感。EGCG 处理 NUGC-3 细胞诱导细胞凋亡，这通过亚 G1 分析、半胱天冬酶-Glo 测定和针对裂解 PARP 和裂解 caspase-3 的 Western blot 得到证实。EGCG 处理降低了 survivin 并增加了 Bax 和 TRAIL 的表达。此外，EGCG 在 NUGC-3 细胞中诱导了 p73 的激活。针对 p73 的小干扰 RNA 减弱了 EGCG 对 survivin 表达和细胞活力的影响。这些结果表明，EGCG 通过抑制 survivin 表达诱导胃癌细胞通过细胞凋亡死亡。该研究提供了一种新的机制，即 EGCG 可能通过 p73 下游抑制 survivin 表达来抑制癌细胞生长，这表明 EGCG 可能是抗 survivin 癌症治疗的潜在候选药物。
