The downregulation of c-Myc and its target gene hTERT is associated with the antiproliferative effects of baicalin on HL-60 cells
The downregulation of c-Myc and its target gene hTERT is associated with the antiproliferative effects of baicalin on HL-60 cells
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c-Myc及其靶基因hTERT的下调与黄芩苷对HL-60细胞的抗增殖作用有关
DOI：
10.3892/ol.2017.7039
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发表时间：
2017-12-01
期刊：
影响因子：
2.9
通讯作者：
Jiang, Guosheng
中科院分区：
文献类型：
--
作者：
Ren, Xia;Zhang, Zhiyong;Jiang, Guosheng
黄芩苷（Baicalin）是从中药黄芩中分离得到的黄酮类化合物，具有抗炎、抗菌、抗焦虑和保肝作用。越来越多的证据表明黄芩苷具有抑制白血病细胞生长、阻滞细胞周期进程、诱导细胞分化或凋亡等抗肿瘤活性。然而，黄芩苷诱导白血病细胞凋亡是否涉及外源性途径以及黄芩苷抗肿瘤活性的机制尚不清楚。本研究通过观察黄芩苷对HL-60细胞凋亡中caspase-8、Fas细胞表面死亡受体（Fas）和Fas配体表达的影响，证实Fas介导的外源性途径也参与了黄芩苷诱导的HL-60细胞凋亡。黄芩苷可使HL-60细胞周期阻滞于G（0）/G（1）期，下调Myc原癌基因蛋白（c-Myc）沿着靶基因端粒酶逆转录酶（hTERT）的表达，从而抑制HL-60细胞的增殖。综上所述，本研究结果表明，黄芩苷能够通过阻断细胞周期的G（0）/G（1）期来抑制HL-60细胞的生长，并通过激活内在和外在途径显着诱导细胞凋亡。HL-60细胞的生长抑制也被证明是通过抑制c-Myc而抑制端粒酶介导的。本研究的结果突出了黄芩苷作为治疗AML的有前途的方案的可能性。
Baicalin is a flavonoid compound isolated from Scutellaria baicalensis, a Chinese traditional medicinal herb, and is used as an anti-inflammatory, antibacterial, anxiolytic and hepatoprotective drug. Accumulating evidence has demonstrated that baicalin exhibits potent antitumor properties by suppressing cell growth, arresting cell cycle progression and inducing differentiation or apoptosis in leukemia cell lines. However, whether or not the extrinsic pathway is involved in baicalin-induced apoptosis of leukemia cells and the mechanisms underlying the antitumor activity of baicalin remain unclear. In the present study, the effect of baicalin on the expression of caspase-8, Fas cell surface death receptor (Fas) and Fas ligand in HL-60 cells was assessed, and it was demonstrated that the Fas-mediated extrinsic pathway was also involved in baicalin-triggered cell apoptosis, in addition to the intrinsic pathway. Furthermore, baicalin was able to inhibit the proliferation of HL-60 cells by arresting the cell cycle at the G(0)/G(1) phase, and by down-regulating Myc proto-oncogene protein (c-Myc) along with its target gene, human telomerase reverse transcriptase. In summary, the results of the present study demonstrated that baicalin was able to inhibit the growth of HL-60 cells through blockade of the G(0)/G(1) phase of the cell cycle, and significantly induce the apoptosis of cells by activating the intrinsic and extrinsic pathways. The inhibition of HL-60 cell growth was also demonstrated to be mediated by telomerase inhibition through suppression of c-Myc. The results of the present study highlight the possibility of baicalin as a promising regimen for the treatment of AML.