Baicalein inhibits the migration and invasive properties of human hepatoma cells
Baicalein inhibits the migration and invasive properties of human hepatoma cells
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DOI：
10.1016/j.taap.2011.07.008
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发表时间：
2011-09-15
影响因子：
3.8
通讯作者：
Kuo, Hsing-Chun
中科院分区：
文献类型：
--
作者：
Chiu, Yung-Wei;Lin, Tseng-Hsi;Kuo, Hsing-Chun
已证明黄酮类化合物对人类的健康有益。我们研究了黄酮类化合物黄芩素是否会抑制人肝癌细胞系的粘附、迁移、侵袭和生长，并探讨了其作用机制。观察黄芩素和黄芩苷对HA 22 T/VGH和SK-Hep 1细胞24 h存活率的影响。为了评估它们的侵袭性，在存在或不存在黄芩素的情况下，将细胞在基质胶包被的transwell膜上孵育。我们研究了黄芩素对细胞粘附的影响，对基质金属蛋白酶（MMPs），蛋白激酶C（PKC）和p38丝裂原活化蛋白激酶（MAPK）的活化，以及对体内肿瘤生长的影响。我们观察到，黄芩素抑制肝癌细胞生长的55%，黄芩素处理的细胞表现出较低的迁移水平比未处理的细胞，细胞侵袭显着降低到28%。与黄芩素孵育的肝癌细胞也显着抑制细胞粘附基质胶，胶原蛋白I，明胶涂层基板。黄芩素还降低基质金属蛋白酶MMP-2、MMP-9和uPA的明胶分解活性，降低p50和p65核转位，并降低磷酸化I-κ-B（IKB）-β。此外，黄芩素降低了PKC α和p38蛋白的磷酸化水平，这些蛋白调节低分化肝癌细胞的侵袭。最后，当SK-Hep 1细胞作为异种移植物在裸鼠中生长时，腹膜内（i. p.）注射黄芩素诱导肿瘤生长的显著剂量依赖性降低。这些结果表明黄芩素的抗癌特性，其中包括抑制粘附，侵袭，迁移和人肝癌细胞在体内的增殖。(C)2011 Elsevier Inc. All rights reserved.
Flavonoids have been demonstrated to exert health benefits in humans. We investigated whether the flavonoid baicalein would inhibit the adhesion, migration, invasion, and growth of human hepatoma cell lines, and we also investigated its mechanism of action. The separate effects of baicalein and baicalin on the viability of HA22T/VGH and SK-Hep1 cells were investigated for 24 h. To evaluate their invasive properties, cells were incubated on matrigel-coated transwell membranes in the presence or absence of baicalein. We examined the effect of baicalein on the adhesion of cells, on the activation of matrix metalloproteinases (MMPs), protein kinase C (PKC), and p38 mitogen-activated protein kinase (MAPK), and on tumor growth in vivo. We observed that baicalein suppresses hepatoma cell growth by 55%, baicalein-treated cells showed lower levels of migration than untreated cells, and cell invasion was significantly reduced to 28%. Incubation of hepatoma cells with baicalein also significantly inhibited cell adhesion to matrigel, collagen I, and gelatin-coated substrate. Baicalein also decreased the gelatinolytic activities of the matrix metalloproteinases MMP-2, MMP-9, and uPA, decreased p50 and p65 nuclear translocation, and decreased phosphorylated I-kappa-B (IKB)-beta. In addition, baicalein reduced the phosphorylation levels of PKC alpha and p38 proteins, which regulate invasion in poorly differentiated hepatoma cells. Finally, when SK-Hep1 cells were grown as xenografts in nude mice, intraperitoneal (i.p.) injection of baicalein induced a significant dose-dependent decrease in tumor growth. These results demonstrate the anticancer properties of baicalein, which include the inhibition of adhesion, invasion, migration, and proliferation of human hepatoma cells in vivo. (C) 2011 Elsevier Inc. All rights reserved.