作　　者： ; ; ; ; ;

机构地区： 南方医科大学

出　　处： 《中华实验外科杂志》 2018年第3期450-452,共3页

摘　　要： 目的探讨姜黄素（Cur）对人结肠癌细胞化疗耐药性的影响和机制。方法采用药物持续接触浓度递增法建立对伊立替康（CPT-11）耐药的人结肠癌细胞株LoVo/CPT-11，细胞计数试剂盒（CCK-8）检测其生长抑制率并计算耐药指数；Western blot检测耐药细胞的肿瘤干细胞（CSC）标志物CD44、CD133的表达变化。不同浓度的Cur（5、10、20 μmol/L）分别联合CPT-11作用于耐药细胞，检测Cur对其耐药性的影响；另耐药细胞设对照组、Cur单药组、CPT-11单药组、混合组，检测各组中CSC标志物变化和CD133＋细胞的比例。结果LoVo/CPT-11细胞的耐药指数为6.21；与LoVo细胞比较，其CD44、CD133在蛋白表达水平均显著上调（1.63±0.42比0.59±0.07、0.75±0.13比0.24±0.02，P＝0.023、0.019）。5、10、20 μmol/L浓度的Cur分别联合CPT-11作用于LoVo/CPT-11细胞，测得CPT-11的半数抑制浓度（IC50）为（144.48±3.22）、（100.72±2.08）、（146.87±2.73） μmol/L，与对照组[（268.72±2.43） μmol/L]比较显著下调（P＝0.031、0.020、0.036）；另外，比较于CPT-11单药组，Cur单药组、混合组中CD44、CD133在蛋白表达水平均显著下调（2.11±0.45、1.79±0.55比3.04±0.64，P＝0.041、0.034；1.34±0.13、0.52±0.04比1.60±0.15，P＝0.044、0.020），并且CD133＋细胞比例分别为（2.91±0.30）%、（1.12±0.15）%，均显著低于CPT-11单药组[（3.53±0.37）%，P＝0.028、0.016]。结论CSC参与人结肠癌细胞化疗耐药性的产生，Cur可通过抑制CSC特性降低人结肠癌细胞的耐药性。 Objective To investigate the effect of curcumin （Cur） onresistance toirinotecan （CPT-11） inhuman colon carcinoma cells and explore the mechanism involved.Methods Drug-resistanthuman colon carcinoma cell line （LoVo/CPT-11） was established by exposure to gradually increased concentrationof CPT-11, cell counting kit-8 （CCK-8） assay was applied to detect the growth inhibition rate and figure up the resistance index. Western blotting was used to examine the change of cancer stem cell （CSC） markers CD44 and CD133. The effect of Cur on resistance to CPT-11 was detected after treatment with the mixture of Cur （5, 10, 20 μmol/L） and CPT-11. Additionally, drug-resistant cells were separatedinto four groups： the control group, the Cur group, the CPT-11 group and the mixture group. The protein expression levels of CSC markers and the proportion of CD133＋ cellswere detectedinthe four groups.Results The resistance index of LoVo/CPT-11 cell was 6.21 and itsprotein expression levels of CD44 and CD133 weresignificantly higher than LoVo cell （1.63±0.42 vs. 0.59±0.07, 0.75±0.13 vs. 0.24±0.02; P=0.023, 0.019）. The 50% inhibition dose （IC50）of CPT-11 in LoVo/CPT-11 cellstreated with Cur （5, 10, 20 μmol/L） and CPT-11 was （144.48±3.22）, （100.72±2.08）, （146.87±2.73） μmol/L respectively, there wassignificant decrease compared with the control group [（268.72±2.43） μmol/L, P=0.031, 0.020, 0.036]. The protein expression levels of CD44 and CD133 in the Cur group and the mixture group were significantly decreased compared with the CPT-11 group （2.11±0.45, 1.79±0.55 vs. 3.04±0.64; P=0.041, 0.034; 1.34±0.13, 0.52±0.04 vs. 1.60±0.15; P=0.044, 0.020）, and the proportion of CD133＋ cells wasalso significantly lower than the CPT-11 group[（2.91±0.29）%, （1.11±0.14）% vs. （3.53±0.37）%; P=0.028, 0.016].Conclusion CSC was related to the acquired chemoresistance of human colon carcinoma cells, Cur could reduce chemoresistance in human colon carcinoma cells by inh

关 键 词： 姜黄素 伊立替康 结肠癌 耐药 肿瘤干细胞

领　　域： []