A potential anti-tumor herbal medicine, Corilagin, inhibits ovarian cancer cell growth through blocking the TGF-β signaling pathways.
A potential anti-tumor herbal medicine, Corilagin, inhibits ovarian cancer cell growth through blocking the TGF-β signaling pathways.
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潜在的抗肿瘤草药科拉拉金通过阻断TGF-β信号传导途径抑制卵巢癌细胞的生长。
DOI：
10.1186/1472-6882-13-33
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发表时间：
2013-02-15
影响因子：
--
通讯作者：
Yu Y
中科院分区：
文献类型：
--
作者：
Jia L;Jin H;Zhou J;Chen L;Lu Y;Ming Y;Yu Y
叶下珠柯里拉京（Corilagin）是一种抗肿瘤活性成分，具有抗肿瘤活性。柯里拉京是单宁家族的一员，已在许多药用植物中发现，并已被用作抗炎剂。然而，柯里拉京抗肿瘤作用的研究报道较少，其抗肿瘤作用机制尚不清楚。本研究的目的是研究柯里拉京在卵巢癌细胞中的抗癌特性。采用磺酰罗丹明B（Sulforhodamine B）细胞增殖实验、流式细胞术和反相蛋白阵列（RPPA）分析Corilagin对卵巢癌细胞株SKOv 3 ip、Hey和HO-8910 PM的作用。将柯里拉京腹膜内递送至携带SKOv 3 ip异种移植物的小鼠。Corilagin抑制卵巢癌细胞系SKOv 3 ip和Hey的生长，IC 50值小于30 μM，同时对正常卵巢表面上皮细胞显示低毒性，IC 50值约为160 μM。Corilagin诱导卵巢癌细胞周期停滞在G2/M期，并增强凋亡。免疫印迹分析表明，Cyclin B1，Myt 1，Phospho-cdc 2和Phospho-Weel在Corilagin处理后下调。柯里拉京处理组的异种移植瘤生长显著低于未处理对照组（P <0.05）。更有趣的是，Corilagin抑制TGF-β分泌到所有测试的卵巢癌细胞系的培养上清液中，并阻断TGF-β诱导的Snail稳定。相比之下，在用细胞毒性药物Paclidone处理的癌细胞中未观察到TGF-β分泌的减少，表明Corilagin特异性靶向TGF-β分泌。Corilagin阻断了经典Smad和非经典ERK/AKT途径的激活。从珠子草中提取的柯里拉京。作为天然有效的治疗剂，通过针对TGF-β/AKT/ERK/Smad信号通路的靶向作用，对抗卵巢癌细胞的生长。
Phyllanthus niruri L. is a well-known hepatoprotective and antiviral medicinal herb. Recently, we identified Corilagin as a major active component with anti-tumor activity in this herbal medicine. Corilagin is a member of the tannin family that has been discovered in many medicinal plants and has been used as an anti-inflammatory agent. However, there have been few reports of the anti-tumor effects of Corilagin, and its anti-tumor mechanism has not been investigated clearly. The aim of the present study is to investigate the anticancer properties of Corilagin in ovarian cancer cells. The ovarian cancer cell lines SKOv3ip, Hey and HO-8910PM were treated with Corilagin and analyzed by Sulforhodamine B (SRB) cell proliferation assay, flow cytometry, and reverse phase protein array (RPPA). Corilagin was delivered intraperitoneally to mice bearing SKOv3ip xenografts. Corilagin inhibited the growth of the ovarian cancer cell lines SKOv3ip and Hey, with IC50 values of less than 30 μM, while displaying low toxicity against normal ovarian surface epithelium cells, with IC50 values of approximately 160 μM. Corilagin induced cell cycle arrest at the G2/M stage and enhanced apoptosis in ovarian cancer cells. Immunoblotting assays demonstrated that Cyclin B1, Myt1, Phospho-cdc2 and Phospho-Weel were down-regulated after Corilagin treatment. Xenograft tumor growth was significantly lower in the Corilagin-treated group compared with the untreated control group (P <0.05). More interestingly, Corilagin inhibited TGF-β secretion into the culture supernatant of all tested ovarian cancer cell lines and blocked the TGF-β-induced stabilization of Snail. In contrast, a reduction of TGF-β secretion was not observed in cancer cells treated with the cytotoxic drug Paclitaxel, suggesting that Corilagin specifically targets TGF-β secretion. Corilagin blocked the activation of both the canonical Smad and non-canonical ERK/AKT pathways. Corilagin extracted from Phyllanthus niruri L. acts as a natural, effective therapeutic agent against the growth of ovarian cancer cells via targeted action against the TGF-β/AKT/ERK/Smad signaling pathways.
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