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白芍总苷体外及体内对人慢性髓系白血病 K562 细胞株的抗肿瘤作用。

Antitumor activity of total paeony glycoside against human chronic myelocytic leukemia K562 cell lines in vitro and in vivo.

机构信息

Department of Immunology, Qiqihar Medical University, Qiqihar 161006, Heilongjiang, People's Republic of China.

出版信息

Med Oncol. 2012 Jun;29(2):1137-47. doi: 10.1007/s12032-011-9909-9. Epub 2011 Mar 31.

DOI:10.1007/s12032-011-9909-9
PMID:21452044
Abstract

To explore the molecular mechanisms of human leukemia cells by total paeony glycoside (TPG), which is extracted from the root of Radix Paeoniae Rubra. The viability of K562 cells was assessed by MTT assay. Flow cytometry was used to detect apoptosis and cell cycle analysis. The changes in intracellular Ca(2+) concentration were determined by fluorescent dye Fluo-3, and mitochondrial membrane potential was determined by the retention of the dye Rh123. The cytoplasmic Bax, Bcl-xL, and Bcl-2 protein expressions were determined by western blot. The mRNA expression of caspase-3, caspase-8, and caspase-9 was detected by RT-PCR. K562 cells were subcutaneously inoculated into nude mice to study the in vivo antitumor effects of TPG. The growth of K562 cells was inhibited and arrested in G0/G1 phase by TPG. TPG also caused apoptosis in K562 cells evidenced by cytosolic accumulation of cytochrome c, caspase-9, and caspase-3. TPG could down-regulate Bcl-2 and Bcl-xL and up-regulate Bax in K562 cells. TPG showed a significant decreased tumor volume and tumor weight in nude mice inoculated with K562 cells. TPG can be developed as a promising anti-chronic myeloid leukemia drug.

摘要

为了探索从赤芍中提取的总芍药苷(TPG)对人白血病细胞的分子机制。通过 MTT 法评估 K562 细胞的活力。采用流式细胞术检测细胞凋亡和细胞周期分析。通过荧光染料 Fluo-3 测定细胞内 Ca(2+)浓度的变化,通过 Rh123 染料保留测定线粒体膜电位。通过 Western blot 测定细胞质 Bax、Bcl-xL 和 Bcl-2 蛋白的表达。通过 RT-PCR 检测 caspase-3、caspase-8 和 caspase-9 的 mRNA 表达。将 K562 细胞皮下接种于裸鼠,研究 TPG 的体内抗肿瘤作用。TPG 抑制 K562 细胞的生长并将其阻滞在 G0/G1 期。TPG 还导致 K562 细胞发生细胞色素 c、caspase-9 和 caspase-3 胞质累积的凋亡。TPG 可下调 K562 细胞中的 Bcl-2 和 Bcl-xL,上调 Bax。TPG 可显著降低裸鼠接种 K562 细胞的肿瘤体积和肿瘤重量。TPG 可开发为一种有前途的抗慢性髓系白血病药物。

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