阿霉素与青蒿素半乳糖苷联合用药对乳腺癌细胞的体外抑制作用及机制

Synergistic Anti-Cancer Activity of the Combination of Artemisinin Glucoside and Doxorubicin in Breast Cancer Cells

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 exhibit potent anti-cancer activities. This study aimed to investigate the anti-proliferative effect of the combination of artemisinin glucoside （AG） and doxorubicin （DOX） on human breast cancer cells. Methods： MTT assay was used to study the anti-proliferative effects and calculate the synergism potential, respectively. Flow cytometry assay was used to detect apoptosis. Western blot analysis was used to detect the protein expression of some apoptosis-related molecules. Results： The proliferation inhibition rate of MCF-7 cell was up to 91.6% after treatment by combination of DOX and AG, which was significantly higher than the same concentration of DOX or AG inhibitory effect （p 〈0.01）. The concentrations of DOX and AG for the best dose ratio were 10 μM and 20 μM respectively. Apoptosis rate of MCF-7 cell in 10 μM DOX ＋20 μM AG group was 19.8%, which was significantly higher than the control and 10 μM DOX or 20 μM AG intervention group. The combinative treatment remarkably activated caspase cascades more than the mono-treatment. Conclusion： Combination of Artemisinin Glucoside and Doxorubicin has a Synergistic Anti-Cancer effect on the breast cancer cells, which may be related with the activation of caspases cascade and cleavage of PARP. This study presented a new opportunity to enhance the effectiveness of future treatment regimens of breast cancer using DOX.