EGCG enhances the therapeutic potential of gemcitabine and CP690550 by inhibiting STAT3 signaling pathway in human pancreatic cancer.
EGCG enhances the therapeutic potential of gemcitabine and CP690550 by inhibiting STAT3 signaling pathway in human pancreatic cancer.
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DOI：
10.1371/journal.pone.0031067
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Srivastava RK
中科院分区：
文献类型：
--
作者：
Tang SN;Fu J;Shankar S;Srivastava RK
信号转导和转录激活因子 3 (STAT3) 是一种癌基因，可促进癌细胞的存活、增殖、运动和进展。靶向 STAT3 信号传导可能会导致人类癌症新治疗方法的开发。在这里，我们检查了表没食子儿茶素没食子酸酯 (EGCG) 对胰腺癌细胞中 STAT3 信号传导的影响，并评估了 EGCG 与吉西他滨或 JAK3 抑制剂 CP690550 (Tasocitinib) 联合治疗和/或预防胰腺癌的治疗潜力。分别通过XTT测定和TUNEL染色测量细胞活力和细胞凋亡。分别通过 qRT-PCR 和蛋白质印迹分析测量基因和蛋白质表达。结果显示，EGCG抑制磷酸化和总JAK3和STAT3的表达、STAT3转录和激活以及STAT3调节基因的表达，从而抑制细胞运动、迁移和侵袭，并诱导caspase-3和PARP裂解。 STAT3 的抑制增强了 EGCG 对细胞运动和活力的抑制作用。此外，吉西他滨和 CP690550 单独抑制 STAT3 靶基因，并与 EGCG 协同抑制细胞活力并诱导胰腺癌细胞凋亡。总体而言，这些结果表明 EGCG 抑制胰腺癌细胞的生长、侵袭和迁移，并通过干扰 STAT3 信号通路诱导细胞凋亡。此外，EGCG进一步增强了吉西他滨和CP690550对抗胰腺癌的治疗潜力。
Signal Transducer and Activator of Transcription 3 (STAT3) is an oncogene, which promotes cell survival, proliferation, motility and progression in cancer cells. Targeting STAT3 signaling may lead to the development of novel therapeutic approaches for human cancers. Here, we examined the effects of epigallocathechin gallate (EGCG) on STAT3 signaling in pancreatic cancer cells, and assessed the therapeutic potential of EGCG with gemcitabine or JAK3 inhibitor CP690550 (Tasocitinib) for the treatment and/or prevention of pancreatic cancer. Cell viability and apoptosis were measured by XTT assay and TUNEL staining, respectively. Gene and protein expressions were measured by qRT-PCR and Western blot analysis, respectively. The results revealed that EGCG inhibited the expression of phospho and total JAK3 and STAT3, STAT3 transcription and activation, and the expression of STAT3-regulated genes, resulting in the inhibition of cell motility, migration and invasion, and the induction of caspase-3 and PARP cleavage. The inhibition of STAT3 enhanced the inhibitory effects of EGCG on cell motility and viability. Additionally, gemcitabine and CP690550 alone inhibited STAT3 target genes and synergized with EGCG to inhibit cell viability and induce apoptosis in pancreatic cancer cells. Overall, these results suggest that EGCG suppresses the growth, invasion and migration of pancreatic cancer cells, and induces apoptosis by interfering with the STAT3 signaling pathway. Moreover, EGCG further enhanced the therapeutic potential of gemcitabine and CP690550 against pancreatic cancer.
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DOI：
10.1186/bcr1680
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Berishaj M;Gao SP;Ahmed S;Leslie K;Al-Ahmadie H;Gerald WL;Bornmann W;Bromberg JF
通讯作者：
Bromberg JF
DOI：
10.1006/bbrc.2000.3297
发表时间：
2000-08-28
影响因子：
3.1
作者：
Ahmad, N;Cheng, PY;Mukhtar, H
通讯作者：
Mukhtar, H
影响因子：
10.5
作者：
Chapman, RS;Lourenco, PC;Watson, CJ
通讯作者：
Watson, CJ
影响因子：
56.9
作者：
Darnell, JE
通讯作者：
Darnell, JE
影响因子：
4.7
作者：
Balasubramanian, Sivaprakasam;Adhikary, Gautam;Eckert, Richard L.
通讯作者：
Eckert, Richard L.