Chinese Clinical Oncology ›› 2018, Vol. 23 ›› Issue (7): 604-609.
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Abstract: ObjectiveTo discuss the effect and mechanism of miR375 on imatinib sensitivity in GISTT1 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. GISTT1 cells were transfected into miR375 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 miR375 in the gastrointestinal stromal tumors and the expression levels of miR375, pVEGFR2, pAkt and PTEN in GISTT1 cells. ResultsThe levels of miR375 in the gastrointestinal stromal tumor tissues and the normal mucosa adjacent to the carcinoma were 0673±0078 and 1000±0101 respectively, and the difference was statistically significant (P<005). The expression of miR375 was positive in 13 cases of gastrointestinal stromal tumors, and the positive expression rate was 289%. After treatment with different concentrations of imatinib (2, 5, 10 μmol/L), the proliferation inhibition rate and apoptosis rate of the transfected group were(2451±210)%,(5239±423)%,(8457±464)% and (1795±366)%,(3542±357)%,(6347±324)%,compared with the negative control group, the difference was statistically significant (P<00 5). After treated with 613 μmol/L imatinib, the expression of miR375 in GISTT1 cells was 2439±0056, which was significantly higher than that of untreated imatinib (1000±0037), and the difference was statistically significant (P<005). After transfection of miR375 mimics, the expression level of pVEGFR2 and pAkt in GISTT1 cells was 212±007 and 182±009 respectively, which was significantly higher than that of the negative control group, and the expression level of PTEN mRNA was 045±012, significantly lower than that of the negative control group, the difference was statistically significant (P<005).The miR375 expressions of GISTT1 cells were positively correlated with pVEGFR2 and pAkt mRNA expressions (r=0689,0465, P<005) and negatively correlated with PTEN mRNA (r=-0523, P<005). ConclusionThere are significant evidences that upregulation miR375 could enhance the sensitivity of gastrointestinal stromal tumor cell to imatinib.
Key words: Gastrointestinal stromal tumor(GIST), MicroRNAs, Imatinib, Sensitivity, Angiogenesis
XU Yongchao, WANG Gangcheng, TANG Ligong, LI Xing, REN Yingkun, LI Jian. . Experimental study of miR375 on imatinib sensitivity in gastrointestinal stromal tumor cells#br#
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http://manu65.magtech.com.cn/Jwk3_lczlxzz/EN/Y2018/V23/I7/604
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