摘要
目的:探讨铁-氟尿嘧啶配合物的抗肿瘤活性和对人胃癌细胞凋亡的影响。方法:采用MTT法检测配合物及其配体对K562、HCT-116、SGC-7901、MCF-7和HEPG-2细胞的增殖抑制作用;Hoechst 33342/PI双染法和流式细胞术检测对人胃癌细胞凋亡的影响;RT-q PCR检测对Caspase-3、Bax、Bcl-2基因表达的影响。结果:配合物作用5株细胞后的IC50值分别为7.8×10-5、5.4×10-5、3.5×10-5、1.1×10-4和2.2×10-5mol/L,能明显抑制细胞的增殖。配合物以10-5mol/L浓度作用SGC-7901细胞36 h后,凋亡率为9.8%,能明显促进SGC-7901细胞凋亡(P<0.01),作用强于其配体5-Fu和Phen(P<0.01);使凋亡相关基因Caspase-3表达上调至4.9(P<0.01);Bcl-2表达下调至0.2(P<0.01)。结论:铁-氟尿嘧啶配合物具有良好的体外抗肿瘤活性,其发挥抗肿瘤作用可能与诱导肿瘤细胞凋亡有关,而其诱导凋亡的作用可能与Caspase-3基因上调和Bcl-2基因下调有关。
Objective: To explore iron- fluorouracil complex's anti- tumor activity and effect to human gastric carcinoma cells apoptosis. Methods: MTT method was used to detect inhibition rate of the complex on tumor cell lines: K562, HCT-116, SGC-7901,MCF-7 and HEPG-2; Hoechst 33342/PI and flow cytometry(FCM)methods were used to exhibit apoptosis of SGC-7901 cells; RTqPCRwas used to measure the mRNA expression of apoptosis related factors: Caspase-3, Bax and Bcl-2. Results: Iron-fluorouracil complex obviously inhibited the proliferation of 5 tumor cell lines. IC50 were 7.8×10-5, 5.4×10-5, 3.5×10-5, 1.1×10-4 and 2.2×10-5 mol/L,respectively. After 36 hours' treatment on SGC-7901 cell with a concentration 10- 5 mol/L, its apoptosis rate was 9.8%, which could promote SGC-7901 cell apoptosis than its ligands 5-Fu and Phen(P<0.01); the mRNA expression of Caspase-3 gene was up-regulated to 4.9(P<0.01), while Bcl-2 was down-regulated to 0.2(P<0.01). Conclusion: The complex showed good anti-tumor activity in vitro, up regulation of Caspase-3 as well as down regulation Bcl-2 may be one of its mechanisms of action.
作者
杜馨娥
周云
陈英杰
施敏
钟文远
周轶平
Du Xin-e;Zhou Yun;Chen Yingjie;Shi Min;Zhong Wenyuan;Zhou Yiping(Pharmaceutical Science, Kunming Medical University, Kunming 650500, China;College of Chemistry, Yunnan Open University,Kunming 650223, China;School of Basic Medicine, Kunming Medical University, Kunming 650500, China;Department of Chemistry, Kunming University, Kunming 650214, China)
出处
《大理大学学报》
CAS
2017年第2期11-19,共9页
Journal of Dali University
基金
云南省科技厅-昆明医科大学应用基础研究联合专项资助项目(2014FB011)
云南省教育厅科学研究基金资助项目(2014Z060)
