Inhibitory effect of Epigallocatechin gallate on ovarian cancer cell proliferation associated with aquaporin 5 expression
Inhibitory effect of Epigallocatechin gallate on ovarian cancer cell proliferation associated with aquaporin 5 expression
复制标题
表没食子儿茶素没食子酸酯对与水通道蛋白5表达相关的卵巢癌细胞增殖的抑制作用
DOI：
10.1007/s00404-011-1942-6
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发表时间：
2012-02-01
影响因子：
2.6
通讯作者：
Chen, Xuejun
中科院分区：
文献类型：
--
作者：
Yan, Chunxiao;Yang, Jianhua;Chen, Xuejun
水通道蛋白5（AQP 5）的异常表达与卵巢癌的浸润、转移及血管生成有关。AQP 5的表达和细胞凋亡与核转录因子NF-κ B B密切相关。本研究以卵巢癌细胞株SKOV 3为研究对象，采用不同浓度的表没食子儿茶素没食子酸酯（Epigallocatechin gallate，EGCG）和NF-κ B特异性抑制剂吡咯烷二硫代氨基甲酸酯（pyrrolidine dithiocarbamate，PDTC）处理SKOV 3细胞不同时间，观察EGCG对SKOV 3细胞增殖的抑制和凋亡的诱导作用，并探讨其对AQP 5表达的影响及其可能机制。MTT法检测细胞增殖情况，DNA Ladder法检测细胞凋亡情况，免疫组化、Western blot和RT-PCR检测AQP 5、NF-κ B p65和I κ B α的表达，并分析其相关性。SKOV 3细胞的生长抑制率呈剂量和时间依赖性逐渐增加。AQP 5、细胞核p65和I κ B α的表达明显降低（P < 0.01）。I kappa B α在SKOV 3细胞胞浆中的表达逐渐增加（P < 0.05），DNA梯状条带显示细胞凋亡。随着PDTC浓度的增加和作用时间的延长，SKOV 3细胞中AQP 5蛋白和mRNA的表达水平下降（P < 0.01）。EGCG对卵巢癌SKOV 3细胞的生长抑制率呈明显的剂量和时间依赖性增加，并能抑制卵巢癌SKOV 3细胞的增殖并诱导其凋亡。EGCG还下调AQP 5的表达，其可能抑制肿瘤生长并与核转录因子NF-κ B相关。
Abnormal expression of aquaporin 5 (AQP5) is associated with ovarian cancer infiltration, metastasis and angiogenesis. AQP 5 expression and apoptosis have been shown to be closely related to nuclear transcription factor NF-kappa B. In this study, we investigated the inhibition of cell proliferation and the induction of apoptosis by Epigallocatechin gallate (EGCG), a potential anti-cancer drug, in the ovarian cancer cell line SKOV3 as well as the effect of EGCG on AQP5 expression and its possible mechanisms.SKOV3 cells were treated with different concentrations of EGCG and the NF-kappa B-specific inhibitor pyrrolidine dithiocarbamate (PDTC) for different times. Cell proliferation was determined using the MTT assay, cell apoptosis was evaluated using the DNA ladder assay, the expression of AQP5, NF-kappa B p65 and I kappa B alpha was detected by immunohistochemistry, western blot analysis and RT-PCR, and the correlation of these protein expression was analyzed.With increasing concentrations of EGCG and prolonged treatment times, the growth inhibition rate of SKOV3 cells gradually increased in a dose- and time-dependent manner. The expression of AQP5 and nuclear p65 and I kappa B alpha was significantly decreased (P < 0.01). The cytoplasmic expression of I kappa B alpha gradually increased (P < 0.05), and the apoptosis of SKOV3 cells was induced as evidenced by typical fragmentation pattern in a DNA ladder assay. With increasing concentrations of PDTC and prolonged treatment times, the protein and mRNA levels of AQP5 in SKOV3 cells decreased (P < 0.01). In addition, the growth inhibition rate of SKOV3 cells significantly increased in a dose- and time-dependent manner.EGCG inhibited the proliferation and induced the apoptosis of ovarian cancer SKOV3 cells. EGCG also down-regulated expression of AQP5, which may inhibit tumor growth and be associated with nuclear transcription factor NF-kappa B.