作　　者： (赵亚新）; (刘洁凡）; (江明华）; (钱海鑫）;

机构地区： 苏州大学附属第一医院普外科,江苏苏州215006 温州医科大学附属第二医院普外科,浙江温州325000

出　　处： 《中国癌症杂志》 2017年第8期648-654,共7页

摘　　要： 背景与目的:肿瘤多药耐药细胞是肿瘤化疗失败的主要原因,也是恶性肿瘤复发、转移等的重要因素。目前发现芹菜素对多种恶性肿瘤细胞具有抗肿瘤作用,但对肿瘤多药耐药细胞的作用研究较少。该研究拟了解芹菜素对乳腺癌多药耐药MCF-7/ADR细胞的作用,初步探讨芹菜素逆转肿瘤多药耐药性的作用。方法:选取人乳腺癌多药耐药MCF-7/ADR细胞为主要研究对象,以芹菜素作用为实验组,以ADR作用为对照组,用MTT法检测细胞生长增殖情况,PI染色法检测细胞周期分布情况,Annexin V/PI法检测细胞凋亡状态情况,MTT法进行体外药物敏感性分析,Rhodamine-123储留检测细胞内药物蓄积和外排情况,采用蛋白[质]印迹法(Western blot)检测细胞内P-gp蛋白的表达情况,采用反转录聚合酶链式反应(reverse transcriptionPCR,RT-PCR)检测多药耐药MDR1基因的转录情况。结果:与对照组相比,芹菜素明显抑制了MCF-7/ADR细胞增殖,阻滞了MCF-7/ADR细胞周期的进展,明显诱导了MCF-7/ADR细胞凋亡的增加;芹菜素作用下ADR对MCF-7/ADR细胞的IC50为(12.37±0.18)μg/m L,明显低于单用ADR对MCF-7/ADR的IC50(39.83±0.29)μg/m L(P<0.05),其逆转倍数为3.22;芹菜素增加了MCF-7/ADR细胞内Rhodamine-123的蓄积;与亲本细胞MCF-7相比,MCF-7/ADR细胞内的MDR1基因为高转录水平、P-gp蛋白为高表达状态;芹菜素作用下MCF-7/ADR细胞内的MDR1基因转录水平和P-gp蛋白的表达水平均下降。结论:芹菜素具有明显的抗MCF-7/ADR细胞作用,同时具有逆转MCF-7/ADR细胞肿瘤多药耐药性功能,其机制可能与降低MDR1基因转录和下调P-gp蛋白介导的药物外转运功能有关。 Background and purpose： Multidrug resistance of tumor cells is the main factor for the failure of chemotherapy. It is found that the apigenin has the anti-tumor efect, but its role in multidrug resistant cells was rarely reported. This study aimed to investigate the efect of apigenin on multidrug resistant breast cancer cell line MCF-7/ADR, and to explore the role of apigenin in reversing multidrug resistance. Methods： The MCF-7/ADR cells were cultured with diferent concentrations of apigenin, and the same cells were cultured with ADR in the control group. The cell proliferation was detected by MTT, the cell cycle distribution was detected by PI, and the cell apoptosis was detect-ed by Annexin V/PI. The drug sensitivity in vitro was detected by the method of MTT, and the drug retention rate was detected by rhodamine 123 accumulation. The expression of P-gp protein was measured by Western blot, the RT-PCR method was used to detect the transcription of multidrug resistance gene MDR1. Results： The MCF-7/ADR cell prolif-eration was inhibited by the apigenin, the cell cycle progression was blocked by the apigenin, and the cell apoptosis was induced by the apigenin. There were signifcant diferences between the apigenin group and the ADR group （P〈0.05）. The IC50 of ADR on MCF-7/ADR cell was （12.37±0.18） μg/mL with the apigenin efect, while the IC50 of ADR on MCF-7/ADR cell was （39.83±0.29） μg/mL without the apigenin effect （P〈0.05）. The reversal index was 3.22. The retention rate of rhodamine 123 in MCF-7/ADR cells in the apigenin group was higher than that in the ADR group. The MDR1 gene transcription level in MCF-7/ADR cells was higher than that in the MCF-7 cells, and the P-gp expression in MCF-7/ADR cells was higher than that in the MCF-7 cells. However, the level of MDR1 gene transcription and P-gp expression were down-regulated by the apigenin in the MCF-7/ADR cells. Conclusion： The apigenin had anti-MCF-7/ADR efect, and played the role of reversing multidrug resistance in the MCF-7

关 键 词： 芹菜素 乳腺癌多药耐药 细胞凋亡 逆转