[关键词]
[摘要]
目的:探索姜黄素与中低剂量化疗药5-氟尿嘧啶(5-FU)联用对胃癌MGC-803细胞生长、细胞凋亡和细胞周期的影响,为临床上应用姜黄素作为胃癌化疗药5-FU的增效剂,以减少5-FU使用剂量、降低其毒副作用提供实验依据。方法:应用MTT检测法检测药物作用对MGC-803细胞的抑制作用;应用基于AO/EB双染的荧光显微观察法和FITC/PI双染的流式细胞技术检测药物作用对MGC-803细胞凋亡的影响;应用基于PI单染的流式细胞技术检测药物作用对MGC-803细胞周期的影响。结果:姜黄素(25 μmol·L-1)分别与低剂量(2.4 μmol·L-1)和中剂量(4.8 μmol·L-1)的5-FU联合作用能有效地抑制MGC-803细胞的生长,诱导细胞凋亡并将细胞周期阻滞在S期,并呈剂量-时间的依赖关系。姜黄素与低剂量5-FU联用组的效果显著优于中剂量(4.8 μmol·L-1)5-FU单用组(P < 0.01),而姜黄素与中剂量5-FU联用组的效果显著优于高剂量(9.6 μmol·L-1)5-FU单用组(P< 0.01),提示姜黄素能显著增强5-FU抗胃癌MGC-803细胞的作用,并呈剂量-时间的依赖关系。结论:本研究为临床上应用姜黄素作为5-FU治疗胃癌的辅助用药,以减少5-FU的使用剂量,从而降低其毒副作用提供了初步的实验依据。
[Key word]
[Abstract]
This study was aimed to provide experimental evidence for clinical application of curcumin to strengthen the effect of 5-Fluorouracil (5-FU) in gastric cancer treatment, so as to reduce the dose of 5-FU and its side-effect in the future treatment. MTT assay was used to detect medication effect on MGC-803 cell growth inhibition; AO/EB double staining fluorescence microscopic observation and FITC/PI double staining flow cytometry were used to detect medication effect on cell apoptosis. Flow cytometry was based on PI staining used to detect medication effect on MGC-803 cell cycle. The results showed that curcumin (25 μmol·L-1) with low-dose (2.4 μmol·L-1) and middle-dose (4.8 μmol·L-1) 5-FU can effectively inhibit MGC-803 cell growth, induce cell apoptosis and block cell cycle in S phase. Which showed dose-time dependent manner. The combined use of curcumin with low-dose 5-FU was more effective than the middle-dose (4.8 μmol·L-1) 5-FU alone (P < 0.01); similarly, the combined use of curcumin with middle-dose 5-FU was more effective than the use of high-dose (9.6 μmol·L-1) 5-FU alone (P < 0.01). It indicated that curcumin can enhance the antitumor effect of 5-FU against MGC-803 cells in a dose-time dependent manner. It was concluded that the study provided a preliminary experimental basis for using curcumin as an adjuvant to 5-FU with the benefit of reducing its dose and toxicity in the clinical treatment of gastric cancer.
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[基金项目]
湖北省科技厅自然科学基金面上项目(2013CFB067):姜黄素联合氟尿嘧啶诱导胃癌细胞凋亡的效应与机理研究,负责人:赵刚。