Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, China.
Acta Pharmacol Sin. 2011 Nov;32(11):1402-10. doi: 10.1038/aps.2011.97. Epub 2011 Oct 10.
To investigate the efficacy of mitomycin C (MMC) in combination with curcumin in suppressing human breast cancer in vitro and in vivo.
Human breast cancer MCF-7 cells were used. Cell viability was measured using MTT assay. The cell cycle phase was detected with flow cytometric analysis. Cell cycle-associated proteins were examined using Western blot analysis. MCF-7 breast cancer xenografts were established to monitor tumor growth and cell cycle-associated protein expression.
Curcumin inhibited MCF-7 breast cancer cell viability in a concentration-dependent manner (IC(50) value=40 μmol/L). Similarly, MMC inhibited the cell viability with an IC(50) value of 5 μmol/L. Combined treatment of MMC and curcumin showed a synergistic antiproliferative effect. In the presence of curcumin (40 μmol/L), the IC(50) value of MMC was reduced to 5 μmol/L. In MCF-7 xenografts, combined administration of curcumin (100 mg/kg) and MMC (1-2 mg/kg) for 4 weeks produced significantly greater inhibition on tumor growth than either treatment alone. The combined treatment resulted in significantly greater G(1) arrest than MMC or curcumin alone. Moreover, the cell cycle arrest was associated with inhibition of cyclin D1, cyclin E, cyclin A, cyclin-dependent kinase 2 (CDK2) and CDK4, along with the induction of the cell cycle inhibitor p21 and p27 both in MCF-7 cells and in MCF-7 xenografts. These proteins were regulated through p38 MAPK pathway.
The results suggest that the combination of MMC and curcumin inhibits MCF-7 cell proliferation and cell cycle progression in vitro and in vivo via the p38 MAPK pathway.
研究丝裂霉素 C（MMC）联合姜黄素抑制人乳腺癌细胞的体内外疗效。
采用人乳腺癌 MCF-7 细胞，MTT 法检测细胞活力，流式细胞术检测细胞周期，Western blot 法检测细胞周期相关蛋白。建立 MCF-7 乳腺癌异种移植瘤模型，监测肿瘤生长和细胞周期相关蛋白的表达。
姜黄素呈浓度依赖性抑制 MCF-7 乳腺癌细胞活力（IC50 值=40 μmol/L），MMC 的 IC50 值为 5 μmol/L。MMC 和姜黄素联合治疗具有协同的抗增殖作用，在姜黄素（40 μmol/L）存在的情况下，MMC 的 IC50 值降低至 5 μmol/L。在 MCF-7 异种移植瘤中，姜黄素（100 mg/kg）联合 MMC（1-2 mg/kg）治疗 4 周，对肿瘤生长的抑制作用明显大于单独治疗。与单独用药相比，联合用药可显著增加 G1 期阻滞，且细胞周期阻滞与 cyclin D1、cyclin E、cyclin A、cyclin-dependent kinase 2（CDK2）和 CDK4 的抑制以及细胞周期抑制剂 p21 和 p27 的诱导有关，这些蛋白通过 p38 MAPK 通路调节。
结果表明，MMC 和姜黄素联合抑制 MCF-7 细胞的增殖和细胞周期进程，其作用机制可能与 p38 MAPK 通路有关。
