姜黃素是從姜科植物姜黃,、莪術(shù)、郁金等根莖中提取的一種天然有效成分,，其腫瘤作用于1985年由印度學(xué)者Kuttan首次提出,，近年來，姜黃素對(duì)多種腫瘤細(xì)胞的產(chǎn)生,、增殖,、轉(zhuǎn)移均有抑制作用機(jī)理被發(fā)現(xiàn)。美國國立腫瘤研究所將其列為第3代腫瘤治療藥,。
11月29 日的《中國藥理學(xué)報(bào)》雜志（Acta Pharmacologica Sinica）刊登了上海中醫(yī)藥大學(xué)蘇式兵教授課題組的研究論文"Curcumin enhanced antiproliferative effect of mitomycin C in human breast cancer MCF-7 cells in vitro and in vivo”,，該課題組發(fā)現(xiàn)姜黃素和絲裂霉素C協(xié)同作用，可提高絲裂霉素C治療乳腺癌效果,。
蘇式兵指出,，女性發(fā)病率最高的惡性腫瘤乳腺癌，尚缺乏理想的治療藥物,。臨床上應(yīng)用的化療藥物主要有絲裂霉素等,，但這些化學(xué)合成藥物毒副作用大，影響生活質(zhì)量,，同時(shí)易產(chǎn)生耐藥性,。因此，尋找一個(gè)能夠“增效減毒”藥物成為研究熱點(diǎn),。
蘇式兵課題組利用裸鼠模型發(fā)現(xiàn),，姜黃素與絲裂霉素C配伍后，降低了絲裂霉素C的用藥劑量,，同時(shí)可以降低單獨(dú)運(yùn)用絲裂霉素C產(chǎn)生的腎毒性和骨髓抑制,。研究人員指出，該研究在臨床上具有廣闊應(yīng)用價(jià)值,，對(duì)促進(jìn)姜黃素這一傳統(tǒng)中藥的研究與開發(fā)具有現(xiàn)實(shí)意義,。（生物谷Bioon.com）
doi:10.1038/aps.2011.97
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PMID:
Curcumin enhanced antiproliferative effect of mitomycin C in human breast cancer MCF-7 cells in vitro and in vivo
Qian-mei ZHOU#, Xiu-feng WANG#, Xin-jun LIU, Hui ZHANG, Yi-yu LU, Shi-bing SU*
Aim: To investigate the efficacy of mitomycin C (MMC) in combination with curcumin in suppressing human breast cancer in vitro and in vivo.Methods: 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.Results: Curcumin inhibited MCF-7 breast cancer cell viability in a concentration-dependent manner (IC50 value=40 μmol/L). Similarly, MMC inhibited the cell viability with an IC50 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 IC50 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 G1 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.Conclusion: 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.
