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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OA北大核心CSTPCD

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

中文摘要英文摘要

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5~80 μg·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20 μg·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 80 μg·mL-1for GIST-T1 and GIST-T1/IMR cells.20 μg·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 1 300 up-regulated genes and 1 609 down-regulated genes in imatinib-resistant cells.The 50%inhibiting concentration values of Curcumin on GIST-T1 and GIST-T1/IMR cells were(15.33±1.36)and(10.49±2.12)μg·mL-1,respectively.In GIST-T1 cells,the IL-6 levels in experimental group and control group were(3.45±0.01)and(5.64±0.42)pg·mL-1;the ROS levels were(2 841.42±81.83)and(4 174.32±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(4 706.40±146.71)and(8 254.34±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 G1 phase,further shortens S phase and G2 phase.Conclusion Curcumin can inhibit the secretion of inflammation and regulate the proliferation of GIST.

陈燕;李雨珂;王茹静;肖洪涛;石三军

成都中医药大学药学院,四川成都 611137||四川省肿瘤临床医学研究中心、四川省肿瘤医院研究所、四川省癌症防治中心、电子科技大学附属肿瘤医院药学部,四川成都 610041成都中医药大学药学院,四川成都 611137四川省肿瘤临床医学研究中心、四川省肿瘤医院研究所、四川省癌症防治中心、电子科技大学附属肿瘤医院药学部,四川成都 610041

中医学

姜黄素;炎症;白细胞介素-6;胃肠道间质瘤;细胞增殖

Curcumin;inflammation;interleukin-6;gastrointestinal stromal tumor;cell proliferation

《中国临床药理学杂志》 2024 (008)

1160-1164 / 5

中国药学会医院药学专业委员会科研专项基金资助项目(CPA-Z05-ZC-2022-002);四川省肿瘤医院青年优秀基金资助项目(YB2023026);四川省抗癌协会临床科研基金资助项目[(齐鲁)HX2023-自由探索002]

10.13699/j.cnki.1001-6821.2024.08.015

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