Chinese Clinical Oncology ›› 2018, Vol. 23 ›› Issue (7): 604-609.

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Experimental study of miR375 on imatinib sensitivity in gastrointestinal stromal tumor cells#br#
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  1. Department of General Surgery, Henan Cancer Hospital Affiliated Hospital of Zhengzhou University, Henan Cancer Hospital
  • Online:2018-07-30 Published:2018-08-30

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

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