Pterostilbene suppresses human endometrial cancer cells in vitro by down-regulating miR-663b
Pterostilbene suppresses human endometrial cancer cells in vitro by down-regulating miR-663b
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DOI：
10.1038/aps.2017.60
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发表时间：
2017-05
影响因子：
8.2
通讯作者：
Yali Wang;Yuan Shen;Jianping Xu;Kun Han;Yan Zhou;Su Yang;Jun-yi Yin;D. Min;Hai-Yan Hu
中科院分区：
文献类型：
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作者：
Yali Wang;Yuan Shen;Jianping Xu;Kun Han;Yan Zhou;Su Yang;Jun-yi Yin;D. Min;Hai-Yan Hu
白藜芦醇一直被认为是一种抗氧化剂和化学预防剂。与白藜芦醇类似，紫檀芪（PT）也是从葡萄属物种中提取的酚类化合物。然而，关于PT的抗肿瘤作用的研究很少。因此，我们研究了PT对体外培养的子宫内膜癌（EC）细胞的作用及其相关的分子机制。PT（25-100 μmol/L）处理EC细胞株HTB-111和石川，呈剂量依赖性地抑制细胞活力，诱导细胞凋亡。使用miR微阵列，我们检查了在有或没有PT的石川细胞中的miR表达谱，并显示miR-663 b在PT处理的石川细胞中减少最多。此外，我们预测并验证了促凋亡因子BCL 2L 14是miR-663 b的直接靶点。过表达miR-663 b和敲低BCL 2L 14可抵消PT对HTB-111和石川细胞的抑制作用。此外，我们使用原位杂交技术评估了51例患者EC组织中的miR-663 b水平。以miR-663 b评分的中位数为界值，将这些EC患者分为两组，miR-663 b高表达的患者预后明显较差。
Resveratrol has long been known as an antioxidant and a chemopreventive agent. Similar to resveratrol, pterostilbene (PT) is also a phenolic compound extracted from the Vitis species. However, there are few studies on the antitumor effect of PT. Thus, we investigated the effects of PT on the endometrial cancer (EC) cells in vitro and the related molecular mechanisms. Treatment of EC cell lines HTB-111 and Ishikawa with PT (25–100 μmol/L) dose-dependently suppressed the cell viability and induced apoptosis. Using miR microarrays, we examined the miR expression profile in Ishikawa cells with or without PT, and revealed that miR-663b was the most decreased in PT-treated Ishikawa cells. Furthermore, we predicted and verified that the pro-apoptosis factor BCL2L14 is the direct target of miR-663b. Over-expression of miR-663b and knock-down of BCL2L14 counteracted the suppressing effects of PT on HTB-111 and Ishikawa cells. In addition, we evaluated the miR-663b levels in EC tissues of 51 patients using an in situ hybridization technique. With the median of the score of miR-663b as a cut-off value, these EC patients were divided into two groups, and the patients with high miR-663b expression had significantly poor prognosis.