Huaier aqueous extract inhibits proliferation of breast cancer cells by inducing apoptosis
Huaier aqueous extract inhibits proliferation of breast cancer cells by inducing apoptosis
复制标题
槐耳水提取物通过诱导细胞凋亡抑制乳腺癌细胞增殖
DOI：
10.1111/j.1349-7006.2010.01680.x
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发表时间：
2010-11-01
期刊：
影响因子：
5.7
通讯作者：
Yang, Qifeng
中科院分区：
文献类型：
--
作者：
Zhang, Ning;Kong, Xiaoli;Yang, Qifeng
近年来，怀耳毛栓菌水提物常用于中国的抗癌辅助治疗，但其抗癌作用机制尚不清楚。在本研究中，我们旨在研究其对MCF-7和MDA-MB-231细胞的抑制作用，并探讨其抗癌作用的可能机制。分别用四甲基偶氮唑盐比色法、侵袭实验、迁移实验和划痕实验检测细胞活力和运动能力。流式细胞仪分析细胞周期分布，PI-Annexin-V染色和罗丹明123法检测细胞周期，免疫印迹法检测细胞凋亡途径。结果表明，怀耳提取物对MCF-7和MDA-MB-231细胞有较强的抑制作用，且呈时间和剂量依赖关系，但对MDA-MB-231细胞的作用更为敏感。此外，细胞的侵袭和迁移也被抑制与淮耳提取物接触。我们还发现，怀耳可以选择性地诱导MCF-7细胞G0/G1期停滞、P53积聚和激活。令人振奋的是，PI-Annexin-V染色和Western印迹分析证实细胞凋亡是由caspase-3执行的。罗丹明123检测线粒体膜电位降低，bcl2下调和bcl2相关X蛋白(Bax)上调，表明怀耳通过线粒体途径诱导细胞凋亡。泛型半胱氨酸氨基转移酶抑制剂Z-VAD-fmk证实了半胱氨酸天冬氨酸氨基转移酶在淮耳诱导的细胞凋亡过程中的激活。正如预期的那样，该抑制剂减少了怀尔诱导的两种细胞系的凋亡。根据我们的研究结果，怀耳可以诱导ER阳性和ER阴性乳腺癌细胞株的细胞凋亡，是乳腺癌治疗的有效辅助剂。(《癌症科学》2010；101：2375-2383)
Aqueous extract of Trametes robiniophila murr (Huaier) has been commonly used in China for cancer complementary therapy in recent years; however, the mechanisms of its anticancer effects are largely unknown. In the present study, we aim to investigate its inhibitory effect on both MCF‐7 and MDA‐MB‐231 cells, and explore the possible mechanisms of its anticancer effect. Cell viability and motility were measured by MTT and invasive assays, migration and scratch assays in vitro, respectively. The distribution of cell cycle, PI‐Annexin‐V staining and Rhodamine 123 assay were analyzed by flow cytometry, and western blot were used to test the apoptotic pathways. We found that Huaier extract could strongly inhibit cell viability of MCF‐7 and MDA‐MB‐231 cells in a time‐ and dose‐dependent manner; however, MDA‐MB‐231 cells showed more susceptibility to the treatment. Furthermore, cell invasiveness and migration were also suppressed with exposure to Huaier extract. We also indicated that Huaier could induce G0/G1 cell‐cycle arrest, p53 accumulation and activation selectively in MCF‐7 cells. Inspiringly, the PI‐Annexin‐V staining assay and western blot analysis confirmed cell apoptosis executed by caspase‐3. Decreased mitochondrial membrane potential by Rhodamine 123 assay and down‐regulation of Bcl‐2 and up‐regulation of BCL2‐associated X protein (BAX) indicated that Huaier induced apoptosis through the mitochondrial pathway. Caspase activation during Huaier‐induced apoptosis was confirmed by pan‐caspase inhibitor, Z‐VAD‐fmk. As expected, the inhibitor decreased Huaier‐induced apoptosis in both cell lines. Based on our findings, Huaier can induce cell apoptosis in both ER‐positive and ER‐negative breast cancer cell lines and is an effective complementary agent for breast cancer treatment. (Cancer Sci 2010; 101: 2375–2383)