miR375与胃肠间质瘤细胞伊马替尼敏感性关系的实验研究#br#

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摘要/Abstract

摘要： 目的探讨miR375与胃肠间质瘤细胞对伊马替尼敏感性的关系以及可能的作用机制。
方法收集2017年1月至2018年2月在河南省肿瘤医院病理科存档的石蜡包埋45例胃肠间质瘤（GIST）组织标本和对应的癌旁正常胃黏膜组织标本。向GISTT1细胞中分别转染miR375 mimics（转染组）或空质粒（阴性对照组），采用MTT法和流式细胞术检测两组细胞增殖和凋亡活性。采用荧光定量PCR法（QPCR）分别检测GIST组织中miR375水平和GISTT1细胞中miR375、pVEGFR2、pAkt、PTEN表达水平。
结果GIST组织和癌旁正常黏膜组织中miR375 水平分别为0673±0078和1000±0101，差异有统计学意义（P＜005）。13例GIST组织中miR375表达呈阳性，阳性表达率为289％。经不同浓度伊马替尼（2、5、10 μmol／L）处理后，转染组细胞增殖抑制率和凋亡率分别为（2451±210）％、（5239±423）％、（8457±464）％和（1795±366）％、（3542±357）％、（6347±324）％，与阴性对照组比较，差异有统计学意义（P＜005）。经613 μmol／L伊马替尼作用后，GISTT1细胞miR375表达量为2439±0056，显著高于未经伊马替尼处理的1000±0037，差异有统计学意义（P＜005）。经miR375 mimics转染后，GISTT1细胞中pVEGFR2和pAkt表达水平分别为212±007、182±009，明显高于阴性对照组，而PTEN mRNA表达水平为045±012，显著低于阴性对照组，差异有统计学意义（P＜005）。miR375与pVEGFR2、pAkt mRNA表达水平呈正相关性（r=0689，0465， P＜005），与PTEN mRNA呈负相关性（r=-0523， P＜005）。
结论上调miR375可增加VEGFR2和Akt磷酸化水平，从而提高GIST细胞对伊马替尼的敏感性。

关键词: 胃肠间质瘤, 微小核糖核酸, 伊马替尼, 敏感性, 血管生成

Abstract: ObjectiveTo discuss the effect and mechanism of miR375 on imatinib sensitivity in GISTT1 gastrointestinal stromal tumor （GIST） cell.
MethodsFrom January 2017 to February 2018， 45 specimens of gastrointestinal stromal tumors and corresponding normal gastric mucosa specimens were collected from the pathology department of Henan Cancer Hospital. GISTT1 cells were transfected into miR375 mimics （transfection group） or empty plasmid （negative control group） respectively. The proliferation and apoptosis activity of the two groups were detected by MTT and flow cytometry. Fluorescence quantitative PCR （QPCR） was used to detect the level of miR375 in the gastrointestinal stromal tumors and the expression levels of miR375， pVEGFR2， pAkt and PTEN in GISTT1 cells.
ResultsThe levels of miR375 in the gastrointestinal stromal tumor tissues and the normal mucosa adjacent to the carcinoma were 0673±0078 and 1000±0101 respectively， and the difference was statistically significant （P＜005）. The expression of miR375 was positive in 13 cases of gastrointestinal stromal tumors， and the positive expression rate was 289％. After treatment with different concentrations of imatinib （2， 5， 10 μmol／L）， the proliferation inhibition rate and apoptosis rate of the transfected group were（2451±210）％，（5239±423）％，（8457±464）％ and （1795±366）％，（3542±357）％，（6347±324）％，compared with the negative control group， the difference was statistically significant （P＜00 5）. After treated with 613 μmol／L imatinib， the expression of miR375 in GISTT1 cells was 2439±0056， which was significantly higher than that of untreated imatinib （1000±0037）， and the difference was statistically significant （P＜005）. After transfection of miR375 mimics， the expression level of pVEGFR2 and pAkt in GISTT1 cells was 212±007 and 182±009 respectively， which was significantly higher than that of the negative control group， and the expression level of PTEN mRNA was 045±012， significantly lower than that of the negative control group， the difference was statistically significant （P＜005）.The miR375 expressions of GISTT1 cells were positively correlated with pVEGFR2 and pAkt mRNA expressions （r=0689，0465， P＜005） and negatively correlated with PTEN mRNA （r=-0523， P＜005）.
ConclusionThere are significant evidences that upregulation miR375 could enhance the sensitivity of gastrointestinal stromal tumor cell to imatinib.

Key words: Gastrointestinal stromal tumor（GIST）, MicroRNAs, Imatinib, Sensitivity, Angiogenesis

徐勇超, 王刚成, 唐礼恭, 李星, 任莹坤, 李剑. miR375与胃肠间质瘤细胞伊马替尼敏感性关系的实验研究#br#

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[J]. 临床肿瘤学杂志, 2018, 23(7): 604-609.

XU Yongchao, WANG Gangcheng, TANG Ligong, LI Xing, REN Yingkun, LI Jian. . Experimental study of miR375 on imatinib sensitivity in gastrointestinal stromal tumor cells#br#

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[J]. Chinese Clinical Oncology, 2018, 23(7): 604-609.

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