The Expression Of STAT3 In Gastrointestinal Stromal Tumors And Its Efect On The Sensitivity To Treatment With Imatinib

Objective:1.To explore the cell Signal transduction And transcriptional activation factor3(Signal Transducer and Activator Of Transcription3 STAT3)in Gastrointestinal Stromal tumor(Gastrointestinal Stromal Tumors GISTs)with differences in tissue And cancer adjacent tissues And the expression Of STAT3 And risk Of Gastrointestinal Stromal tumor grading correlation relationship with survival.2.Reduce the expression level of STAT3 in GIST-T1cell line,and observe the effect of its changes on the drug sensitivity of imatinib.Methods:(1)Immunohistochemistry was applied to detect 106 cases of archivist wax blocks that underwent complete resection of stromal tumors in people’s hospital of guangxi zhuang autonomous region from 2016 to 2018,none of which had received imatinib or received relevant treatment before surgery.Confirmed by pathology were gastrointestinal stromal tumors(GISTs),while detecting stromal tumor adjacent tissues of 47 cases(cut edge>2 cm).(2)The expression of STAT3 in GIST-T1 cell lines was detected by Western Blot(WB).(3)The expression of STAT3 in GIST-T1 cell lines was reduced by lentivirus transfection,and the transfection was verified by western-blot.(4)MTT method was used to detect the difference in the inhibition rate between GIST-T1 cell lines and the transfected cell lines under the action of imatinib with the same concentration gradient,and statistical analysis was performed and the inhibition rate curve was plotted.(5)Flow cytometry was used to detect the difference in apoptosis rates between GIST-T1 cell lines and transfected cell lines under the same concentration gradient of imatinib.(6)Flow cytometry was used to detect the cell cycle differences between GIST-T1 cell lines and the transfected cell lines.Results:(1)The positive expression rate of STAT3 in gastrointestinal stromal tumor tissues(62/106 58.49%)was significantly higher than that in adjacent tumor tissues(12/4725.53%)(?~2=14.16 P=0.000168<0.05).(2)The expression level of STAT3 protein was significantly correlated with the risk classification of gastrointestinal stromal tumors(P<0.05).(3)Kaplan-Meier analysis showed that patients with high STAT3 protein expression had shorter survival and worse prognosis than patients with low STAT3 protein expression,and the difference was statistically significant(P<0.05).(4)MTT results showed that after reducing STAT3 expression,the inhibition rate of imatinib in the transfection group was significantly increased compared with GIST-T1,indicating a statistically significant difference(F=28.454 P<0.05).(5)Flow cytometry results showed that after STAT3expression was reduced,the apoptosis rate of the transfection group was significantly increased compared with GIST-T1 at the same concentration of imatinib and the difference was statistically significant(F=12.01 P<0.05).(6)For cell cycle,compared with GIST-T1cell lines,the proportion of G1 phase in GIST-transfection was reduced,and the difference was statistically significant(F=5.72 P<0.05).The proportion of G2/M phase increased,and the difference was statistically significant(F=8.499 P<0.05).The proportion of the two strains in the S phase was basically the same,and the difference was not statistically significant(F=0.000037 P>0.05).Conclusion:(1)STAT3 is highly expressed in gastrointestinal stromal tumors and is closely related to risk grade and prognosis of patients.(2)Inhibition of STAT3 can enhance sensitivity of imatinib in the treatment of GISTs,or permission to become the key to solve imatinib secondary resistance.(3)The STAT3 may become the new therapeutic targets and strategies for GISTs of treatment.