【摘要】 目的:研究戊地昔布联合阿霉素对人乳腺癌细胞(MCF-7)增殖的抑制作用及其机制。方法:将人MCF-7细胞随机分为空白对照组、溶剂对照组、阿霉素(0.25mg·L-1)组、戊地昔布(25、50、100μmol·L-1)组及联用组(阿霉素0.25mg·L-1+戊地昔布25、50、100μmol·L-1),加入相应药物继续培养,检测培养24、48、72h(n=6)后各组人MCF-7细胞的增殖抑制率;检测戊地昔布25μmol·L-1时培养48h后各组细胞周期和增殖细胞核抗原(PCNA)蛋白、细胞周期蛋白(CyclinD1)及环氧酶2(COX-2)蛋白表达。结果:与溶剂对照组比较,除戊地昔布25μmol·L-1培养24h外,阿霉素组、戊地昔布组及联用组增殖抑制率均明显增加(P均<0.01),且呈浓度、时间依赖性;与阿霉素组和戊地昔布组比较,联用组增殖抑制率均明显增加(P均<0.01)。戊地昔布组细胞阻滞于G0/G1期,S期细胞比例明显减少(P<0.05);联用组细胞阻滞于G0/G1期和G2/M期。与溶剂对照组比较,戊地昔布组、阿霉素组及联用组PCNA、CyclinD1蛋白表达均明显降低(P<0.05或P<0.01),仅戊地昔布组和联用组COX-2蛋白表达明显降低(P<0.05或P<0.01)。结论:戊地昔布与阿霉素联用具有协同抑制人MCF-7细胞增殖的作用,可能与抑制CyclinD1和PCNA蛋白表达从而阻滞细胞周期有关。更多还原

【Abstract】 OBJECTIVE:To study the inhibition effects of valdecoxib combined with adriamycin on the proliferation of human MCF-7 cells and its mechanism. METHODS:Human MCF-7 cells were randomly divided into blank control group,solvent control group,adriamycin group(0.25 mg·L-1) ,valdecoxib group(25,50,100 μmol·L-1) and combination group(adriamycin 0.25 mg·L-1+valdecoxib 25,50,100 μmol·L-1) . The inhibition rates of human MCF-7 cell proliferation were determined 24,48,72 h after treated with relevant medicine(n=6) . Cell cycle,the protein expressions of PCNA,Cyclin D1 and COX-2 in various groups were detected 48 h after cultured in valdecoxib 25 μmol·L-1. RESULTS:Compared with sdvent control group,the inhibition rate of cell proliferation was increased significantly in adriamycin group,valdecoxib group and combination group,except for culture of valdecoxib 25 μmol·L-1 for 24 h(all P<0.01) ,in concentration and time-dependant manner;compared with adriamycin group and valdecoxib group,the inhibition rate of cell proliferation was increased significantly in combination group(all P<0.01) . Valdecoxib markedly blocked the MCF-7 cell progression by arresting the cells in the G0/G1 phase,and the percentage of cells in S phase decreased dramatically(P<0.05);and valdecoxib combined with adriamycin blocked the MCF-7 cell progression by arresting the cells in G0/G1 and G2/M phase(P<0.05) . Compared with solvent control group,the protein expressions of PCNA and Cyclin D1 in valdecoxib group,adriamycin group and combination group were decreased significantly(P<0.05 or P<0.01) ,while the protein expression of COX-2 in valdecoxib group and combination group decreased significantly(P<0.05 or P<0.01) . CONCLUSION:Valdecoxib synchronized with adriamycin can inhibit the proliferation of human MCF-7 cells significantly,which may be associated with the inhibition of Cyclin D1 and PCNA expression and the blockage of cell cycle.更多还原