EGCG inhibited bladder cancer T24 and 5637 cell proliferation and migration via PI3K/AKT pathway.
EGCG inhibited bladder cancer T24 and 5637 cell proliferation and migration via PI3K/AKT pathway.
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DOI：
10.18632/oncotarget.24301
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发表时间：
2018-02-23
期刊：
影响因子：
--
通讯作者：
Huang WR
中科院分区：
文献类型：
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作者：
Luo KW;Lung WY;Chun-Xie;Luo XL;Huang WR
表没食子儿茶素-3-没食子酸酯（EGCG）是绿茶中的生物活性多酚，已被证明具有多种生物活性。我们之前发现 EGCG 通过下调 NF-κB 和 MMP-9 抑制 SW780 肿瘤生长。这项研究表明，EGCG 通过 PI3K/AKT 通路抑制膀胱癌 T24 和 5637 细胞的增殖和迁移，而不调节 NF-κB。我们的结果表明，EGCG 处理通过诱导细胞凋亡而显着抑制细胞增殖，且对正常膀胱 SV-HUC-1 细胞没有明显毒性。 25-100 μM EGCG 还抑制 5637 和 T24 细胞迁移和侵袭。 Western blot证实EGCG通过激活caspases-3和PARP诱导T24和5637细胞凋亡。此外，EGCG在T24和5637细胞中上调PTEN并降低磷酸化PI3K、AKT的表达。此外，动物研究表明，与未治疗的对照相比，EGCG（100 mg/kg，每天腹腔注射，持续 4 周）可使携带 T24 肿瘤的小鼠的肿瘤重量降低 51.2%。 EGCG还降低了肿瘤中磷酸化PI3K和AKT的表达，表明PI3K/AKT在EGCG抑制肿瘤生长中的重要作用。当AKT被抑制时，EGCG对T24和5637细胞的细胞迁移没有明显影响。总之，我们的研究阐明了 EGCG 可有效抑制 T24 和 5637 细胞增殖和迁移，并提供证据表明 EGCG 通过调节 PI3K/AKT 通路抑制细胞增殖和肿瘤生长。
Epigallocatechin-3-gallate (EGCG), the bioactive polyphenol in green tea, has been demonstrated to have various biological activities. We previously found that EGCG inhibited SW780 tumor growth by down-regulation of NF-κB and MMP-9. This study demonstrated that EGCG inhibited bladder cancer T24 and 5637 cell proliferation and migration via PI3K/AKT pathway, without modulation of NF-κB. Our results showed that treatment of EGCG resulted in significant inhibition of cell proliferation by induction of apoptosis, without obvious toxicity to normal bladder SV-HUC-1 cells. EGCG also inhibited 5637 and T24 cell migration and invasion at 25–100 μM. Western blot confirmed that EGCG induced apoptosis in T24 and 5637cells by activation of caspases-3 and PARP. Besides, EGCG up-regulated PTEN and decreased the expression of phosphorylated PI3K, AKT in both T24 and 5637 cells. In addition, animal study demonstrated that EGCG (100 mg/kg, i.p. injected daily for 4 weeks) decreased the tumor weight in mice bearing T24 tumors by 51.2%, as compared with the untreated control. EGCG also decreased the expression of phosphorylated PI3K and AKT in tumor, indicating the important role of PI3K/AKT in EGCG inhibited tumor growth. When AKT was inhibited, EGCG showed no obvious effect in cell migration in T24 and 5637 cells. In conclusion, our study elucidated that EGCG was effective in inhibition of T24 and 5637 cell proliferation and migration, and presented evidence that EGCG inhibited cell proliferation and tumor growth by modulation of PI3K/AKT pathway.