蓝萼甲素通过溶酶体-线粒体途径诱导人鳞状口腔上皮癌KB细胞发生凋亡
Glaucocalyxin A induces apoptosis in human squamous cell carcinoma KB cellsthrough lysosomal-mitochondrial death pathway
目的 研究天然产物蓝萼甲素抗肿瘤活性及其诱导肿瘤细胞凋亡的作用机制。方法 采用MTT法进行抗肿瘤活性评价，选择肿瘤细胞株为人白血病细胞株K562，人鳞状细胞癌KB细胞，人乳腺癌细胞MCF-7等。采用annexin V-FITC/PI染色测定凋亡，流式细胞仪测定蓝萼甲素对细胞周期的影响，溶酶体完整性分析（吖啶橙染色），线粒体膜电势分析，细胞色素释放分析，Western blot对凋亡途经相关蛋白分析，caspase-3和caspase-9活性分析。结果蓝萼甲素具有显著的抗肿瘤活性，IC50在3～8.4 μM之间。它能通过诱导肿瘤细胞发生凋亡，阻滞细胞周期，并且增加溶酶体通透性，破坏线粒体途径，上调Bax表达，下调BCL-2表达，并且能活化caspase-3和caspase-9的活性。结论天然提取物蓝萼甲素的诱导肿瘤凋亡的作用可能是通过溶酶体-线粒体途径发生的。
Glaucocalyxin A (GLA) is a biologically active ent-kauranoid diterpenoid isolated from Rabdosia japonicavar glaucocalyx, a traditional Chinese medicinal herb, which has been shown to inhibit tumor cell proliferation. Our results showed that GLA is a powerful growth inhibitor of K562, PC3, MCF-7 and KB cancer cells, IC50 ranged from 3～8.4 μM. Cell flow cytometry of GLA-treated KB cells showed a marked accumulation of cells in the S-phase and G2-phase fraction in a dose-dependent manner. In addition, staining for annexin V/PI, changes in nuclear morphology, and activation of caspase-9 and -3 support a role for apoptosis. Further investigation with squamous cell carcinoma KB cells found that GLA could induce an early lysosomal rupture within 6h as assessed by acridine-orange uptake. Additional experiments revealed that GLA could induce a dose-dependent accumulation of reactive oxygen species (ROS), trigger mitochondrial membrane permeabilization, release cytochrome c, and then down-regulate Bcl-2, up-regulate Bax. These results revealed that the cytoxicity of GLA was involved in a lysosomal-mitochondrial death pathwan
廖凯、孙玲美
肿瘤学细胞生物学生物化学
蓝萼甲素凋亡线粒体溶酶体
Glaucocalyxin Areactive oxygen specieslysosomemitochondriaapoptosis
廖凯,孙玲美.蓝萼甲素通过溶酶体-线粒体途径诱导人鳞状口腔上皮癌KB细胞发生凋亡[EB/OL].(2014-01-16)[2025-07-22].http://www.paper.edu.cn/releasepaper/content/201401-726.点此复制
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