目的研究雷公藤红素对人阿霉素耐药MCF-7/ADR乳腺癌细胞生长的作用。方法采用MTT试验检测MCF-7/ADR细胞对阿霉素的耐药情况以及雷公藤红素对MCF-7/ADR细胞生长的影响;采用Annexin VFITC/PI双染试验分析雷公藤红素对MCF-7/ADR耐药细胞凋亡的诱导作用;应用流式细胞周期分析检测雷公藤红素对MCF-7/ADR耐药细胞周期的影响。结果 MCF-7/ADR细胞对阿霉素耐药指数达14.54;而雷公藤红素能有效抑制阿霉素耐药细胞MCF-7/ADR的生长,并呈现浓度依赖性,作用48 h的IC50是1.04μmol/L,MCF-7/ADR对雷公藤红素的耐药指数仅为0.87。2μmol/L雷公藤红素作用8 h后,Annexin V-FITC染色阳性的MCF-7/ADR细胞比例较对照显著升高,差异有统计学意义(P〈0.05)。在1μmol/L雷公藤红素作用24 h后,G1期细胞比例由对照(59.22±3.78)%升高至(77.44±4.21)%,而S期细胞比例由对照(37.51±2.91)%降至(19.65±2.25)%,差异有统计学意义(P〈0.05)。结论雷公藤红素能激活MCF-7/ADR细胞凋亡的发生,并诱导MCF-7/ADR发生G1/S细胞周期阻滞,从而对阿霉素耐药MCF-7/ADR细胞的生长发挥高效抑制作用。
Objective To investigate the effect of celastrol on the growth of adriamycin-resistant MCF-7/ADR breast cancer cells. Methods The resistance situation of MCF-7/ADR cells to adriamycin and the effect of celastrol on the growth of adriamycin-resistant MCF-7/ADR cells were evaluated by MTT assay. The effect of celastrol on apoptosis in MCF-7/ADR breast cancer cells was determined by annexin V-FITC/PI double staining. The effect of celastrol on cell cycle progression was determined by flow cytometry analysis. Results The resistance index of MCF-7/ADR cells to adriamycin was14. 54. After treatment with celastrol for 48 h,MCF-7/ADR cells displayed markedly inhibited growth in a dose-dependent manner,and calculated IC50 was 1. 04 μmol/L. Celastrol decreased the resistance index of MCF-7/ADR from 14. 54 to0. 87. The numbers of apoptotic MCF-7/ADR cells,as revealed by annexin V binding,significantly increased upon celastrol treatment(P〈0. 05). Celastrol treatment caused an increase of cells in G1 phase from(59. 22 ± 3. 78) % to(77. 44 ±4. 21) %,while the percentage of cells in S phase was decreased from(37. 51 ± 2. 91) % to(19. 65 ± 2. 25) %(P〈0. 05).Conclusion These data demonstrated that celastrol induced apoptosis and G1/S cell cycle arrest in MCF-7/ADR cells and consequently displayed potent cytocidal effect on adriamycin-resistant MCF-7/ADR breast cancer cells.