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人参皂苷Rh2逆转肺腺癌细胞对顺铂耐药机制的研究

[Research on the mechanism of ginsenoside Rh2 reversing the resistance of lung adenocarcinoma cells to cisplatin].

作者信息

Hu Shuo, Yu Jian-Ying, Xiong Ling-Jing, Hu Cheng-Ping, Zhang Yong-Xue

机构信息

Postdoctoral Research Station of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Scinece and Technology, Wuhan 430022, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2010 Jan 26;90(4):264-8.

Abstract

OBJECTIVE

To explore the mechanism of ginsenoside Rh2 in reversing the resistance of lung adenocarcinoma cells to cisplatin.

METHODS

In the Rh2, DDP and DDP + Rh2 group A549DDP cells were treated with Rh2, cisplatin, cisplatin + Rh2 respectively for 48 hours. In the control group the A549DDP cells were not treated with any kind of drugs. The state of mitochondrial permeability transition pore (PTP) was evaluated by ultra violate spectrofluorometer. Concentration of calcium in cells, membrane potential of mitochondrion and apoptosis cells were determined by flow cytometry. The expression of cyt-c and Caspase-3 was estimated by Western blots. Cellular shapes were observed by fluorescent microscopy.

RESULTS

The concentrations of calcium were similar among the former three groups, but was obviously increased in the Rh2 + DDP group (t = 22.47, P < 0.01). A(540) of mitochondrion among the former three groups were not different, but decreased significantly in the Rh2 + DDP group (t = 8.21, P < 0.01). The membrane potentials of mitochondrion showed no difference in the former groups, that was remarkably lower in the Rh2 + DDP group than in the control group (chi(2) = 46.01, P < 0.01). There was little expression of cty-c and Caspase-3 in the former groups, but high expression of those in the Rh2 + DDP group. Fluorescence was distributed equally on the cells nucleus in the former groups. In the Rh2 + DDP group many cell nucleus shrank or were distorted. The apoptosis rate of the cells was 6.32%, 7.24%, 7.41% and 21.96% in the four groups respectively. Which in Rh2 + DDP group was higher than that in the control group (t = 10.92, P < 0.05).

CONCLUSIONS

The effect of ginsenoside Rh2 reversing resistance of lung adenocarcinoma A549DDP cells to cisplatin can be performed by apoptotic mitochondria pathway.

摘要

目的

探讨人参皂苷Rh2逆转肺腺癌细胞对顺铂耐药的机制。

方法

将Rh2组、DDP组和DDP + Rh2组的A549DDP细胞分别用Rh2、顺铂、顺铂 + Rh2处理48小时。对照组的A549DDP细胞不做任何药物处理。用紫外分光荧光计评估线粒体通透性转换孔(PTP)的状态。通过流式细胞术测定细胞内钙浓度、线粒体膜电位和凋亡细胞。用蛋白质免疫印迹法评估细胞色素c(cyt-c)和半胱天冬酶-3(Caspase-3)的表达。通过荧光显微镜观察细胞形态。

结果

前3组的钙浓度相似,但Rh2 + DDP组明显升高(t = 22.47,P < 0.01)。前3组线粒体的A(540)无差异,但Rh2 + DDP组显著降低(t = 8.21,P < 0.01)。前几组线粒体膜电位无差异,但Rh2 + DDP组明显低于对照组(χ(2) = 46.01,P < 0.01)。前几组cyt-c和Caspase-3表达较少,但Rh2 + DDP组表达较高。前几组荧光均匀分布在细胞核上。Rh2 + DDP组许多细胞核缩小或变形。4组细胞凋亡率分别为6.32%、7.24%、7.41%和21.96%。Rh2 + DDP组高于对照组(t = 10.92,P < 0.05)。

结论

人参皂苷Rh2可通过线粒体凋亡途径逆转肺腺癌A549DDP细胞对顺铂的耐药性。

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