摘要
目的合成并评价碘化亚油酸（ILA）、碘化亚油酸5-氟尿嘧啶核昔偶联酯（IFU）在体内外对肝细胞癌的抑制作用。方法ILA和IFU均通过化学合成及纯化，并经’H核磁谱证实。用不同浓度的ILA、IFU、5-氟尿嘧啶（5-FU）和传统碘油分别处理两株人肝癌细胞：SMMC-7721和QGY-7703，检测72h细胞存活率，并计算50％抑制浓度（IC50）和90％抑制浓度（IC90）。经SMMC-7721肝癌细胞皮下接种成功的30只裸鼠随机分成5组：ILA组、IFU组、5-FU组、传统碘油组和二甲基亚砜（DMSO）组（对照组），并分别1次瘤内注射100ul的ILA、IFu、5-FU、传统碘油和DMSO，4周后计算抑瘤率。组间比较用t检验。结果对SMMC-7721细胞，ILA、IFU和5-FU的IC50分别为134．38μmol／L、17．55μmol／L、7．38μmol／L；IC90分别为192．88μmol／L、97．63μmol／L、大于200μmol／L。对QGY-7703细胞，ILA、IFU和5-FU的Ic50分别为109．55μmol／L、44．79μmol／L、98．06μmol／L；IC90三者均大于200μmol／L。对SMMC-7721和QGY-7703细胞，传统碘油IC50均大于400μmol／L。与DMSO对照组抑瘤率0比较，ILA组、IFU组和5-FU组的抑瘤率分别为31．90％、56．90％、31．04％，统计值t分别为2．37、4．91、2．59，P值均小于0．05，差异均有统计学意义。而IFU组抑瘤率高于ILA组和5-FU组，传统碘油组抑瘤率为0．87％，未见抑瘤活性。结论ILA和IFU均可在体内、外抑制肝癌细胞增殖，并且IFU的抑瘤作用强于ILA。
Objective To explore the potential of iodized linoleic acid （ILA） and its 5-ftuoro- deoxyuridine ester （IFU） to inhibit hepatocellular carcinoma （HCC） cells in vitro and tumors in vivo. Methods ILA and its constituent component IFU were chemically synthesized, purified, and confirmed by 1H-NMR. The HCC cell lines, QGY-7703 （5-fluorouracil （5-FU） treatment sensitive） and SMMC-7721 （5-FU resistant）, were treated with ILA, IFU, 5-FU, or traditional lipiodol for 72 hours. Survival rates of the treated cells were assessed by the methyl thiazolyl tetrazolium method, and used to calculate the IC50 and IC90. In addition, thirty nude mice were subcutaneously inoculated with SMMC-7721 cells and randomly divided two weeks later into four treatment groups （n = 6 each） for intra-tumoral injection of ILA, IFU, 5-FU, lipiodol or DMSO （controls）. The rate of tumor inhibition （RTI） was calculated for each group at week 4 after treatment. Results For the cultured SMMC-7721 cells, the inhibitory concentrations for ILA, IFU, and 5-FU were： IC50： 134.38 μmaol/L, 17.55 μmol/L, and 7.38μmol/L; IC90：192.88 μmol/L, 97.63 μmol/L, and 〉 200 μmol/L. For the cultured QGY-7703 cells, the inhibitory concentrations for ILA, IFU, and 5-FU were： IC50：109.55μmol/L, 44.79 btrnoFL, and 98.06 μrnol/L; IC90＂ all, 〉 200 μmol/L. In both cell types, the IC50 of lipiodol was 〉 400 μmol/L. Compared with the RTI of the control mice （100%）, the RTI of ILA-treated mice was 31.9% （t = 2.37, P 〈 0.05）, of IFU-treated mice was 56.9% （t = 4.91,P 〈 0.01）, and of 5-FU-treat^d, mice was 31.0% （t = 2.59, P 〈 0.05）. The RTI of IFU was significantly stronger than that of either ILA or 5-FU （P 〈 0.05）. The lipiodol treatment showed no inhibition effect on tumors （P 〉 0.05）. Conclusion ILA and IFU can effectively inhibit the growth of HCC cells in vitro and tumors in vivo. Furthermore, IFU outperforms ILA in inhibiting HCC growth.
出处
《中华肝脏病杂志》
CAS
CSCD
北大核心
2013年第5期372-375,共4页
Chinese Journal of Hepatology
基金
上海市科委医学引导类课题（10411961600）
上海市卫生局青年课题（20114y193）
关键词
癌
肝细胞
半数抑制浓度
亚油酸
氟尿嘧啶
小鼠
裸
Carcinoma, hepatocellular
Inhibitory concentration 50
Linoleic acid
Fluorouracil
Mice, nude
