金丝桃素联合紫杉醇通过上调胞内ROS水平抑制乳腺癌细胞生长

Hypericin Combined with Paclitaxel Inhibits Breast Cancer Cells Through Up-regulation ROS Level

关键词:  乳腺癌  金丝桃素  紫杉醇  联合用药

Key words:  breast cancer  hypericin  paclitaxel  combination therapy

摘要:

目的 研究紫杉醇联合金丝桃素对乳腺癌细胞增殖的影响。方法 利用乳腺癌细胞株MCF-7和Bcap-37为研究对象，分别进行单药及联合用药，通过MTT法检测药物对肿瘤细胞增殖活性的影响；通过流式细胞技术检测药物对肿瘤细胞凋亡的影响；通过对线粒体膜电位、凋亡相关caspase-3蛋白表达量、ROS含量、还原型谷胱甘肽含量变化及谷胱甘肽S转移酶活性等进行检测。结果 紫杉醇（0.5 mg·L^–1）与金丝桃素（0.5 mg·L^–1）联合，作用24 h，在MCF-7及Bcap-37细胞中的协同指数Q分别为1.30和1.41，表现出良好的药物协同效应。2种细胞的线粒体膜电位明显下降，凋亡相关蛋白caspase-3表达水平及胞内ROS水平升高，而还原型谷胱甘肽水平降低，谷胱甘肽S转移酶活性受到抑制。结论 联合使用紫杉醇与金丝桃素的光动力疗法可以强化药物对乳腺癌细胞MCF-7以及Bcap-37的杀伤作用，促进细胞凋亡，为乳腺癌的组合疗法奠定了细胞实验基础。

Abstract:

OBJECTIVE To study the effect of paclitaxel combined with hypericin on breast cancer cell proliferation. METHODS Breast cancer cells MCF-7 and Bcap-37 were set as study objects. The effects of single drug and combination drug on the proliferation activity of cancer cells were detected by MTT method. The effect of drugs on cancer cell apoptosis was detected by flow cytometry. The changes of mitochondrial membrane potential, the expression level of caspase-3 protein, the content of ROS, the content of reduced glutathione and the activity of glutathione S-transferase were detected in this study. RESULTS When incubation cells with 0.5 mg·L^-1 paclitaxel combined with 0.5 mg·L^-1 hypericin for 24 h, the synergistic index Q in MCF-7 and Bcap-37 cells was 1.30 and 1.41, respectively, it showed good cooperative effect. In the two kinds of cells, mitochondrial membrane potential was significantly decreased, the expression level of caspase-3 and intracellular ROS increased, while the reduced glutathione level decreased, and the activity of glutathione S-transferase was inhibited. CONCLUSION Paclitaxel combined with hypericin-photodynamic therapy enhance the proliferation inhibition on breast cancer cells MCF-7 and Bcap-37, which prove the cell experiment foundation for combination therapy of breast cancer.