IR-780联合阿霉素对肝癌干细胞样细胞的杀伤效应研究

发布时间：2018-02-08 14:18

本文关键词： IR- 阿霉素肝肿瘤肿瘤干细胞细胞毒性　出处：《第三军医大学学报》2017年12期 　论文类型：期刊论文

【摘要】：目的探讨七甲川花菁类荧光小分子IR-780联合阿霉素对肝癌干细胞样细胞的杀伤作用。方法利用CCK-8试剂盒检测不同浓度IR-780(0、1.250、2.500、5.000、10.000、20.000μmol/L)及IR-780联合阿霉素(0、0.025、0.050、0.100、0.200、0.400μmol/L)对4种不同肝癌细胞(QGY-7703、SMMC-7721、Huh-7和Hep G2)的杀伤效应,并确定后续实验IR-780和阿霉素的浓度,采用细胞划痕实验检测IR-780联合阿霉素对肝癌细胞迁移能力的影响;采用无血清悬浮培养的方法从Huh-7细胞株中分离并鉴定出具有干细胞特性的肿瘤细胞,检测IR-780联合阿霉素对肝癌干细胞样细胞的杀伤作用及迁移能力的影响;在裸鼠皮下荷瘤模型中观察IR-780联合阿霉素对肝癌干细胞样细胞生长的抑制作用。结果低浓度的IR-780对肝癌细胞无明显杀伤作用;采用1.250μmol/L的IR-780联合阿霉素可对多种肝癌细胞产生较强的杀伤作用,其中半数致死浓度LC50较单药阿霉素降低25%;采用无血清悬浮培养的方法培养出Huh-7细胞肿瘤球,比较其与贴壁细胞的克隆形成能力、致瘤能力和细胞周期分布,证明悬浮培养的肿瘤细胞具有肿瘤干细胞特性;IR-780联合阿霉素对肝癌干细胞样细胞具有较强的杀伤作用,单用阿霉素和IR-780联合阿霉素对肝癌干细胞样细胞的LC50差异有统计学意义[(0.30±0.02)vs(0.22±0.04)μmol/L,P0.05];IR-780联合阿霉素可明显抑制肝癌干细胞样细胞的迁移能力和裸鼠皮下肿瘤的生长。结论 IR-780可增强阿霉素的抗肿瘤作用,提高对肝癌干细胞样细胞的杀伤效应。
[Abstract]:Objective to investigate the cytotoxicity of heptachuan cyanine fluorescent small molecule IR-780 combined with adriamycin on hepatocellular carcinoma stem cell like cells. Methods CCK-8 kit was used to detect the cytotoxicity of different concentrations of IR-7800.2502.5002.5000.0000.0000.000 渭 mol / L) and IR-780 combined with doxorubicin 0.0500.1000.2000.400 渭 mol / L to four different kinds of hepatoma cell line QGY-7703SMMC-7721h- Huh-7. The killing effect of Hep G2, The concentrations of IR-780 and adriamycin were determined and the effect of IR-780 combined with doxorubicin on the migration of hepatoma cells was detected by cell scratch assay. Tumor cells with stem cell characteristics were isolated and identified from Huh-7 cell lines by serum-free suspension culture. The effects of IR-780 combined with adriamycin on the cytotoxicity and migration of hepatoma stem cell-like cells were detected. The inhibitory effects of IR-780 combined with adriamycin on the growth of hepatoma stem cell-like cells were observed in nude mice. Results low concentration of IR-780 had no significant killing effect on hepatoma cells. 1.250 渭 mol/L of IR-780 combined with adriamycin could produce strong killing effect on many kinds of hepatoma cells, in which the LD50 of LC50 was 25% lower than that of single drug adriamycin, and the tumor spheres of Huh-7 cells were cultured by serum-free suspension culture. Compared with the adherent cells, the tumor cells had the characteristics of tumor stem cells. IR-780 combined with adriamycin had a strong killing effect on hepatoma stem cell-like cells. The difference of LC50 between adriamycin and IR-780 combined with adriamycin on hepatoma stem cell like cells was significant [0.30 卤0.02 IR-780 0.22 卤0.04 渭 mol / L P 0.05] IR-780 combined with doxorubicin could significantly inhibit the migration of hepatoma stem cell-like cells and the growth of subcutaneous tumor in nude mice. Can enhance the antitumor effect of adriamycin, To increase the killing effect on hepatoma stem cell like cells.
【作者单位】：第三军医大学军事预防医学院全军复合伤研究所创伤、烧伤与复合伤国家重点实验室;第三军医大学新桥医院全军肿瘤研究所;
【基金】：国家自然科学基金重点项目(81130026) 重庆市研究生创新课题(2014年)~~
【分类号】：R735.7

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