目的 研究姜黄素增强伊立替康对结肠癌SW620细胞的体外抑制作用,并探讨其作用机制。方法 MTT法检测不同质量浓度伊立替康和姜黄素单用或联合用药对SW620细胞增殖的影响;流式细胞仪检测不同质量浓度伊立替康和姜黄素单用或联合用药对SW620细胞凋亡的影响,比较细胞凋亡率;采用蛋白质印记法检测不同质量浓度伊立替康和姜黄素单用或联合用药对SW620细胞内拓扑异构酶I蛋白表达水平的影响。结果 伊立替康和姜黄素单用均对SW620细胞增殖具有抑制作用,呈浓度和时间相关性。5、50 μg/mL伊立替康分别与0~30 μg/mL姜黄素联合处理SW620细胞12、24、48 h均具有协同抑制细胞活性的作用,且呈浓度和时间相关性。高质量浓度比低质量浓度的伊立替康与姜黄素联合用药抑制效果显著(P<0.01)。0、20 μg/mL姜黄素分别与0、5、50 μg/mL伊立替康联合处理SW620细胞12、24、48 h,姜黄素可以增强伊立替康诱导的SW620细胞凋亡率。20 μg/mL姜黄素联合5、50μg/mL伊立替康显著上调了SW620细胞内拓扑异构酶-Ⅰ蛋白的表达,协同诱导了SW620细胞内拓扑异构酶-Ⅰ蛋白的表达。结论 伊立替康联合姜黄素可以协同增强对SW620细胞活性的抑制作用,协同诱导SW620细胞凋亡,其作用机制可能与伊立替康、姜黄素上调拓扑异构酶-Ⅰ表达有关。

ObjectiveTo investigate inhibitory effect of curcumin combined with irinotecan growth of colon cancer SW620 cells and explore its mechanism. Methods After treated by various concentrations of curcumin and irinotecan alone or both, the cell proliferations of SW620 cell were detected by MTT assay. Effect of various concentrations of curcumin combined with irinotecan or alone on apoptosis of SW620 cell were studied by flow cytometry and apoptosis rates were compared. The topoisomerase I protein expression levels in the cell were analyzed by Western blotting method. Results Curcumin or irinotecan had inhibition on cell proliferation by concentration- and time-dependent manners. There were synergistic inhibitions against SW620 cell viability treated by 5 and 50 μg/mL curcumin combined with 0 - 30 μg/mL irinotecan for 12, 24, and 48 h in concentration and time dependent manner. There were significant differences between high and low concentrations of irinotecan combined with curcumin (P < 0.01). After treated by 0 and 20 μg/mL curcumin combined with 0, 5, and 50 μg/mL irinotecan on SW620 cells for 12, 24, and 48 h, curcumin could enhance SW620 cell apoptosis rates induced by irinotecan. Curcumin (20 μg/mL) combined with 5 and 50 μg/mL irinotecan could significantly up-regulate the expression of topoisomerase I protein in SW620 cells, and synergetically induce the expression of topoisomerase I protein. Conclusions Irinotecan combined with curcumin can synergetically enhance inhibition against colon cancer SW620 cells, induce SW620 cell apoptosis, which may be related to up-regulation of the expression of topoisomerase I protein in SW620 cells by irinotecan and curcumin.

天津市卫生局科技基金项目(2012KY20)