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中国癌症防治杂志 ›› 2021, Vol. 13 ›› Issue (2): 170-176.doi: 10.3969/j.issn.1674-5671.2021.02.10

• 基础研究 • 上一篇    下一篇

沉默IGFBP-1对人胃肠道间质瘤GIST882细胞生长的影响及其作用机制 

  

  1. 新疆维吾尔自治区人民医院胃肠外科;新疆医科大学附属肿瘤医院宁养院;新疆医科大学附属肿瘤医院乳腺头颈外科
  • 出版日期:2021-04-25 发布日期:2021-04-30
  • 通讯作者: 李涛 E-mail:weiliu20191113@163.com

Effect of silencing IGFBP?1 on the growth of human gastrointestinal stromal tumor cells GIST882 and its mechanism

  • Online:2021-04-25 Published:2021-04-30
  • Supported by:
    新疆维吾尔自治区自然科学基金项目(2018D01C195)

摘要: 目的 探讨胰岛素样生长因子结合蛋白1(IGFBP-1)在人胃肠道间质瘤中的表达及其对胃肠道间质瘤细胞生长的影响和作用机制。方法 采用免疫组化染色检测IGFBP-1表达;人胃肠道间质瘤细胞GIST882分别转染siRNA-NC(siRNA-NC组)、siRNA-IGFBP-1(siRNA-IGFBP-1组),并设置空白对照组。采用qRT-PCR和Western blot实验检测IGFBP-1 mRNA和蛋白表达水平;CCK-8实验检测细胞活性;EDU实验检测细胞增殖能力;Annexin V-FITC/PI染色检测细胞凋亡情况;Transwell小室实验检测细胞迁移与侵袭能力;Western blot检测PI3K/AKT/mTOR信号通路相关蛋白的表达。结果 胃肠道间质瘤组织中IGFBP-1阳性表达率高于癌旁组织(P<0.05);与空白对照组和siRNA-NC组比较,siRNA-IGFBP-1组细胞中IGFBP-1 mRNA和蛋白相对表达量均降低(均P<0.05);IGFBP-1沉默后细胞增殖活性下降,EDU阳性细胞率降低,凋亡率增加,迁移与侵袭细胞数目均减少(均P<0.05);p-PI3K/PI3K、p-AKT/AKT及p-mTOR/mTOR比值下降(均P<0.05)。结论 沉默IGFBP-1表达可抑制胃肠道间质瘤细胞增殖、迁移与侵袭,并促进细胞凋亡,其机制可能与抑制PI3K/AKT/mTOR信号通路激活相关。

关键词: 胃肠道间质瘤, 胰岛素样生长因子结合蛋白1, 增殖, 凋亡, 迁移, 侵袭

Abstract: Objective To investigate the expression of insulin-like growth factor binding protein 1 (IGFBP-1) in human gastrointestinal stromal tumors, and its effect on the growth of gastrointestinal stromal tumor cells as well as its underlying mechanism. Methods The expression of IGFBP-1 was detected by immunohistochemical staining.The human gastrointestinal stromal tumor cells GIST882 were transfected with siRNA-NC (siRNA-NC group) and siRNA-IGFBP-1 (siRNA-IGFBP-1 group), respectively, and blank control group was set. The mRNA and protein expression level of IGFBP-1 were detected by qRT-PCR and the Western blot; the cell viability was detected by the CCK-8 experiment; the cell proliferation ability was detected by the EDU test; the cell apoptosis was detected by Annexin V-FITC/PI staining; the cell migration and invasion ability was detected by Transwell chamber experiment, and the expression of PI3K/AKT/mTOR signaling pathway-related proteins was detected by the Western blot. Results The positive expression rate of IGFBP-1 in gastrointestinal stromal tumor tissues was higher than that in adjacent tissues (P<0.05). Compared with the blank control group and the siRNA-NC group, the relative expression of IGFBP-1 mRNA and protein in siRNA-IGFBP-1 group were decreased (all P<0.05). After IGFBP-1 silencing, the cell proliferation activity decreased, the EDU positive cells rate decreased, the apoptosis rate increased, and the number of migrating and invading cells decreased (both P<0.05); and the ratios of p-PI3K/PI3K, p-AKT/AKT and p-mTOR/mTOR decreased (all P<0.05). Conclusions Silencing IGFBP-1 expression can inhibit the cell proliferation, migration, invasion of gastrointestinal stromal tumor, and promote cell apoptosis, which may be related to the inhibition of PI3K/AKT /mTOR signal pathway activation.

Key words: Gastrointestinal stromal tumor, Insulin-like growth factor binding protein 1, Proliferation, Apoptosis, Migration, Invasion

中图分类号: 

  • R735.2