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目的:青蒿素及其衍生物具有抗癌活性,本研究旨在探讨阿霉素(DOX)与青蒿素半乳糖苷(AG)联合用药对乳腺癌细胞的体外抑制作用及机制。方法:DOX与AG联合对乳腺癌MCF-7细胞株进行干预,MTT法评价二者对癌细胞增殖的影响;流式细胞计量术检测细胞凋亡;免疫印迹法检测凋亡相关蛋白表达情况。结果:DOX与AG联合作用对MCF-7细胞增殖抑制率最高可达91.6%,均显著高于同浓度DOX或AG抑制效果(P<0.01),且浓度分别为10μM和20μM量效比最佳。10μM DOX+20μM AG联合干预组癌细胞凋亡率为19.8%,显著高于对照组及单用10μM DOX或20μM AG干预组。DOX与AG联合给药比单独应用其中一种均更加显著激活caspase级联信号通路,进而更加有效的促进癌细胞凋亡。结论:DOX和AG联合用药对人乳腺癌MCF-7细胞具有协同抑制效应,其机制可能与caspase家族介导的蛋白酶级联反应以及PARP裂解失活有关。这项研究为提高DOX治疗乳腺癌的有效性提供了新的思路。
OBJECTIVE: Artemisinin and its derivatives have anticancer activity. The purpose of this study was to investigate the inhibitory effect of doxorubicin (DOX) and artemisinin galactoside (AG) on breast cancer cells in vitro and its mechanism. Methods: DOX and AG were used to interfere MCF-7 breast cancer cells. MTT assay was used to evaluate the effect of both on proliferation of cancer cells. Flow cytometry was used to detect the apoptosis of MCF-7 cells. Western blotting was used to detect the expression of apoptosis related proteins. Results: The highest inhibitory rate of DOX and AG on MCF-7 cells was 91.6%, which was significantly higher than that of DOX or AG at the same concentration (P <0.01), and the best dose-effect was 10μM and 20μM . The apoptosis rate of cancer cells in combination with 10μM DOX + 20μM AG was 19.8%, which was significantly higher than that in control group and only 10μM DOX or 20μM AG intervention group. Administration of DOX and AG more significantly stimulated the caspase cascade than either alone, which further promoted the apoptosis of cancer cells. CONCLUSION: The combination of DOX and AG has a synergistic inhibitory effect on human breast cancer MCF-7 cells. The mechanism may be related to caspase-mediated protease cascade and PARP cleavage and inactivation. This study provides a new way to improve the effectiveness of DOX in the treatment of breast cancer.