IQGAP1 overexpression inhibits the chemosensitivity of esophageal squamous cell carcinoma cells to cisplatin
In order to investigate whether overexpression or interference of IQ motif containing GTPase-activating protein 1(IQGAP1)affects cisplatin chemosensitivity in esophageal squamous cell carcinoma,stable cell lines with IQGAP1 overexpression and IQGAP1 interference were constructed by plasmid transfection and detected by Western blot.Then,the cells were treated with different concentrations of cisplatin(2.5 μmol/L,5 μmol/L,10 μmol/L,20 μmol/L,40 μmol/L).The cell viability of IQGAP1 overexpression,IQGAP1 interference and control cells was detected by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide(MTT)assay.The apoptosis rates were detected by 4',6-Diamidino-2-phenylindole(DAPI)staining and flow cytometry.And the expression levels of apoptosis-related protein were detected by Western blot.Stable cell lines with IQGAP1 overexpression and IQGAP1 interference were successfully established.After treatment with cisplatin at different concentrations,the result of MTT assay showed that the viability of IQGAP1 overexpression cells was significantly higher than that of control cells,and the viability of IQGAP1 interference cells was significantly lower than that of control cells(P＜0.05).DAPI staining and flow cytometry assay showed that the apoptosis rate of IQGAP1 overexpression cells was significantly lower than that of control cells,and the apoptosis rate of IQGAP1 interference cells was significantly higher than that of control cells(P＜0.05).The Western blot results showed that the expression levels of pro-cysteinyl aspartate specific proteinase-3(Procaspase-3)and poly ADP-ribose polymerase(PARP)in IQGAP1 overexpression cells were higher than those of control cells,and the expression levels of cleaved-PARP were lower than those of control cells.The expression levels of Procaspase-3 and PARP in IQGAP1 interference cells were lower than those of control cells.In summary,IQGAP1 can affect the sensitivity of tumor cells to cisplatin by inhibiting cell apoptosis,which suggests that the IQGAP1 overexpression is a molecular mechanism of cisplatin resistance in esophageal squamous cell carcinoma cells.Moreover,knockdown of IQGAP1 expression can improve the sensitivity of tumor cells to cisplatin chemotherapy,suggesting that IQGAP1 may be an important therapeutic target to improve the chemosensitivity of esophageal squamous cell carcinoma.
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