CLIC1 Promote Cervical Cancer SiHa Cells Migration And Invasion Through ROS/ERK Signaling Pathway

Objective:Cervical cancer is the most common malignant tumor of female reproductive system.Recent studies have found that some patients with cervical cancer may suffer recurrence and metastasis after radical surgery.In recent years,many studies have found that the expression of chloride intracellular channel 1(CLIC1)is up-regulated in many malignant tumors and is related to the metastasis of malignant tumors.Previous experiments have demonstrated that CLIC1 regulated intracellular reactive oxygen species(ROS)production under hypoxic-reoxygenated(H-R)conditions,so it participates in cervical cancer metastasis and its mechanism.This experiment intends to study the role of CLIC1 in the migration and invasion of cervical cancer SiHa cells through ROS / ERK signal pathway,which provide a new treatment ideas and solutions for the prevention and treatment of cervical cancer.Methods:Human cervical cancer SiHa cells cultured H-R were respectively treated with IAA94,DPI,NAC or PD98059.Western-Blot dectect the relative protein expression of CLIC1,p-ERK,MMP-2,and MMP-9.Cell scratch assay and Transwell invasion assay detect the effects on cervical cancer SiHa cell migration and invasion ability.Finally,using the SPSS22.0 software for statistical anlysis and processing.Results:1.The relative expression of p-ERK protein in the H-R group(6.60 ± 0.04)was significantly higher than that in the normoxia group(1.00 ± 0.02),and the relative expression of p-ERK ? MMP-2 and MMP-9 protein in the H-R+DPI group and the H-R+NAC group(2.83±0.02,1.86±0.01,3.59±0.03)were significantly lower than that of p-ERK?MMP-2 and MMP-9 protein in the H-R group(6.60±0.04,3.67±0.04,5.83 ± 0.02).The relative expression of p-ERK ? MMP-2 and MMP-9 protein in the H-R+IAA94 group and the H-R+PD98059 group(4.05±0.03,2.67±0.02,3,48±0.03)were lower than that of p-ERK?MMP-2 and MMP-9 protein in the H-R group(6.60±0.04,3.67±0.04,5.83±0.02),there were statistically significant(P<0.01).2.The scratch healing area(61.76 ± 0.52)of SiHa cells in the H-R group was significantly higher than that the normoxia group(41.94 ± 1.18),while the scratch healing area in the H-R+DPI group and the H-R+NAC group(49.34 ±2.15,49.21 ±3.31)were significantly lower than that in the H-R group(61.76 ± 0.52).The scratch healing area of the H-R+ IAA94 group and H-R+ PD98059 group(50.53±3.18,49.90±6.28)were lower than that in the H-R group(61.76±0.52),and those differences were all statistically significant(P<0.01).3.Compared with the normoxia group,the number of SiHa cells in the H-R group(91.80±10.9)was significantly higher than that in the normoxia group(46.60±6.19),and the number of SiHa cells in the H-R+DPI group and the H-R+NAC group(65.20±9.58,64.40 ± 6.80)were significantly lower than that in the H-R group(91.80 ±10.9).While the number of cells in the H-R+IAA94 group and H-R+PD98059 group(69.20±9.88,59.00 ±7.81)were also significantly lower than that in the H-R group(91.80±10.9),and those differences were statistically significant(P<0.01).Conclusion:CLIC1 plays an important role in SiHa cell metastasis of cervical cancer,and in the H-R environment,it activates ROS / ERK signal pathway by regulating the production of ROS in cells,so as to accelerate the migration and invasion of cervical cancer SiHa cells.