20(S)-ginsenoside Rh2 inhibits the proliferation and induces the apoptosis of KG-1a cells through the Wnt/β-catenin signaling pathway
20(S)-ginsenoside Rh2 inhibits the proliferation and induces the apoptosis of KG-1a cells through the Wnt/β-catenin signaling pathway
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DOI：
10.3892/or.2016.4774
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发表时间：
2016-07-01
期刊：
影响因子：
4.2
通讯作者：
Chen, Di-Long
中科院分区：
文献类型：
--
作者：
Chen, Yi;Liu, Ze-Hong;Chen, Di-Long
先前的研究表明，人参总皂苷（TSPG）和其他人参皂苷单体抑制白血病细胞的增殖。然而，这一效果尚未在它们之间进行比较。采用细胞计数试剂盒-8检测细胞活力，透射电镜下观察细胞超微结构特征。流式细胞术检测细胞周期分布及凋亡情况。采用实时荧光定量pcr、western blotting和免疫荧光法检测β -catenin、TCF4、cyclin Dl和NF-KBp65的表达。ChIP-PCR检测β -catenin/TCF4靶基因的转录情况。我们发现20(S)-人参皂苷Rh2 [(S)Rh2]比其他单体更有效地抑制KG-la细胞的增殖。此外，(S)Rh2在GO/G1期阻滞KG-la细胞并诱导凋亡。β -连环蛋白、TCF4、cyclin D1 mRNA和蛋白水平降低。ChIP-PCR结果显示(S)Rh2下调β -catenin/TCF4靶基因cyclin Dl和c-myc的转录。这些结果表明(S)Rh2通过Wnt/ β -catenin信号通路诱导细胞周期阻滞和凋亡，显示了其作为白血病化疗药物的潜力。
Previous research has shown that total saponins of Panax ginseng (TSPG) and other ginsenoside monomers inhibit the proliferation of leukemia cells. However, the effect has not been compared among them. Cell viability was determined by Cell Counting Kit-8 assay, and ultra-structural characteristics were observed under transmission electron microscopy. Cell cycle distribution and apoptosis were determined by flow cytometry (FCM). Real-time fluorescence quantitative-PCR, western blotting and immunofluorescence were used to measure the expression of beta-catenin, TCF4, cyclin Dl and NF-KBp65. beta-catenin/TCF4 target gene transcription were observed by ChIP-PCR assay. We found that 20(S)-ginsenoside Rh2 [(S)Rh2] inhibited the proliferation of KG-la cells more efficiently than the other monomers. Moreover, (S)Rh2 arrested KG-la cells in the GO/G1 phase and induced apoptosis. In addition, the levels of beta-catenin, TCF4, cyclin D1 mRNA and protein were decreased. The ChIP-PCR showed that (S)Rh2 downregulated the transcription of beta-catenin/TCF4 target genes, such as cyclin Dl and c-myc. These results indicated that (S)Rh2 induced cell cycle arrest and apoptosis through the Wnt/beta-catenin signaling pathway, demonstrating its potential as a chemotherapeutic agent for leukemia therapy.