RESUMO
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.
RESUMO
Epigallocatechin-3-gallate (EGCG), the bioactive polyphenol in green tea, has been demonstrated to have various biological activities. Our study aims to investigate the antiproliferation and antimigration effects of EGCG against bladder cancer SW780 cells both in vitro and in vivo. Our results showed that treatment of EGCG resulted in significant inhibition of cell proliferation by induction of apoptosis, without obvious toxicity to normal bladder epithelium SV-HUC-1 cells. EGCG also inhibited SW780 cell migration and invasion at 25-100 µM. Western blot confirmed that EGCG induced apoptosis in SW780 cells by activation of caspases-8, -9 and -3, Bax, Bcl-2 and PARP. Besides, animal study demonstrated that EGCG [100 mg/kg, intraperitoneal (i.p.) injection daily for 3 weeks] decreased the tumor volume significantly in mice bearing SW780 tumors, as well as the tumor weight (decreased by 68.4%). In addition, EGCG down-regulated the expression of nuclear factor-kappa B (NF-κB) and matrix metalloproteinase (MMP)-9 in both protein and mRNA level in tumor and SW780 cells. When NF-κB was inhibited, EGCG showed no obvious effect in cell proliferation and migration. In conclusion, our study demonstrated that EGCG was effective in inhibition SW780 cell proliferation and migration, and presented first evidence that EGCG inhibited SW780 tumor growth by down-regulation of NF-κB and MMP-9.
