姜黄素通过抑制炎症因子IL-6调控胃肠道间质瘤细胞的增殖抑制的研究

Curcumin regulates the proliferation inhibition of gastrointestinal stromal tumor cells by inhibiting the inflammatory factor IL-6

目的 探讨姜黄素是否具有作为胃肠道间质瘤(GIST)治疗潜在药物的能力。方法 通过细胞转录学分析伊马替尼耐药细胞与非耐药细胞的差异基因。用5~80μg·mL^(-1)姜黄素作用于GIST-T1及GIST-T1/IMR细胞,用细胞计数试剂-8(CCK-8)法验证姜黄素的抗肿瘤活性。实验组给予20μg·mL^(-1)的姜黄素,对照组给予磷酸盐缓冲溶液。用酶联免疫吸附试验法检测白细胞介素-6(IL-6)、活性氧(ROS)与一氧化氮合酶(iNOS)的含量,用流式细胞术分析细胞周期变化。结果 以非耐药细胞为对比,伊马替尼耐药细胞上存在1 300个上调表达基因,1 609个下调表达基因。姜黄素对GIST-T1及GIST-T1/IMR细胞的半抑制浓度分别为(15.33±1.36)和(10.49±2.12)μg·mL^(-1)。在GIST-T1细胞中,实验组和对照组的IL-6分别为(3.45±0.01)和(5.64±0.42)pg·mL^(-1),ROS分别为(2 841.42±81.83)和(4 174.32±439.12) pg·mL^(-1),iNOS分别为(7.02±0.08)和(8.08±0.03)μmol·L^(-1);在GIST-T1/IMR细胞中,实验组和对照组的IL-6分别为(2.47±0.30)和(6.30±0.01)pg·mL^(-1),ROS分别为(4 706.40±146.71)和(8 254.34±342.35) pg·mL^(-1),iNOS分别为(6.42±0.09)和(7.29±0.04)μmol·L^(-1);在2种细胞中,实验组的上述指标与对照组比较,在统计学上差异均有统计学意义(P<0.05,P<0.01)。姜黄素可阻滞GIST-T1及GIST-T1/IMR细胞周期于G1期,进一步缩短S期与G2期。结论 姜黄素可通过抑制炎症分泌,从而调控GIST增殖。

Objective To investigate whether curcumin is a potential drug for the treatment of gastrointestinal stromal tumors(GIST).Methods The differential genes of imatinib-resistant cells and non-resistant cells were analyzed by cell transcriptology.The antitumor activity of curcumin was verified by cell counting kit-8(CCK-8)method,and the concentration of Curcumin ranged from 5 to 80μg·mL^(-1) for GIST-T1 and GIST-T1/IMR cells.20μg·mL^(-1) Curcumin as the experimental group,phosphate buffered solution as the control group.The contents of interleukin-6(IL-6),reactive oxygen species(ROS)and nitric oxide(NO)were measured by enzyme linked immunosorbent assay.The cell cycle changes were analyzed by flow cytometry.Results Using non-resistant cells as a contrast,the results showed that there were 1300 up-regulated genes and 1609 down-regulated genes in imatinib-resistant cells.The 50%inhibiting concentration values of Curcumin on GIST-T1 and CIST-T1/IMR cells were(15.33±1.36)and(10.49±2.12)μg·mL^(-1),respectively.In CIST-T1 cells,the IL-6 levels in experimental group and control group were(3.45±0.01)and(5.64±0.42)pg:mL-';the ROS levels were(2841.42±81.83)and(4174.32±439.12)pg·mL^(-1);the iNOS levels were(7.02±0.08)and(8.08±0.03)μmol·L^(-1),respectively.In GIST-T1/IMR cells,the IL-6 levels in experimental group and control group were(2.47±0.30)and(6.30±0.01)pg·mL^(-1);the ROS levels were(4706.40±146.71)and(8254.34±342.35)pg·mL^(-1);the iNOS levels were(6.42±0.09)and(7.29±0.04)μmol·L^(-1),respectively.Among the 2 cells,the differences of above indicators were statistically significant between the experimental group and the control group(P<0.05,P<0.01).Curcumin blocked the cell cycle of GIST-T1 and GIST-T1/IMR in G phase,further shortens S phase and G2 phase.Conclusion Curcumin can inhibit the secretion of inflammation and regulate the proliferation of CIST.