LHPP inhibits the proliferation,invasion,and metastasis of colorectal cancer by regulating the activity of the NOX2/SHP2 pathway

DONG Qing; GUO Hao; DING Fei; LI Feng

doi:10.3969/j.issn.1674-4136.2024.02.014

Abstract：Objective To investigate the impact of histidine phosphatase(LHPP)on the proliferation,invasion,and migration of colorectal cancer through the oxidative stress pathway,and to preliminarily elucidate its underlying mechanism.Methods Cell transfection was performed using Liposome3000. Plasmids OE-NC,OE-LHPP,and oligonucleotide fragments si-NC,and si-LHPP were transfected into SW480 cells,and the protein expression levels of LHPP,NOX2,and p-SHP2 were detected by Western Blot.Plasmids OE-NC and OE-LHPP were transfected into SW480 cells with concurrent NCA stimulation,and the protein expression levels of NOX2,p-SHP2,p-PI3K,p-ERK1/2,MMP-9,and Cyclin D1 were examined by Western Blot.Additionally,plasmids OE-NC and OE-LHPP were transfected into SW480 and SW620 cells with NAC treatment,and the migration distance of the cells was measured by scratch assay.The number of cells that migrated through the pores was counted by Transwell assay,and the cell proliferation ability was assessed by colony formation assay.Results In SW480 cells,the expression levels of LHPP and NOX2 proteins in the OE-LHPP group were significantly higher compared to the OE-NC group(P＜0.01),but the expression of p-SHP2 protein was significantly lower than in the OE-NC group(P＜0.01).In SW480 cells,the si-LHPP group had significantly lower expression levels of LHPP and NOX2 proteins compared to the OE-NC group(P＜0.01),while the expression of p-SHP2 protein was significantly higher than in the si-NC group.Compared to the OE-NC group,the NOX2 protein levels in SW480 cells transfected with OE-LHPP significantly increased(P＜0.01),but the expression levels of p-SHP2,p-PI3K,p-ERK1/2,MMP-9,and Cyclin D1 proteins significantly decreased(P＜0.01).Additionally,the migration distance was shortened,the number of cells that migrated through the pores was reduced,and the quantity of cell colonies formed decreased in both SW480 and SW620 cells.After adding NAC,the differences in the expression levels of NOX2,p-SHP2,p-PI3K,p-ERK1/2,MMP-9,and Cyclin D1 between the OE-NC and OE-LHPP groups in SW480 and SW620 cells were eliminated,as were the differences in cell scratch,cell invasion,and cell proliferation.Conclusions LHPP appears to mitigate the progression of colorectal cancer by promoting oxidative stress and inhibiting the SHP2,PI3K,and ERK pathways,thereby suppressing the proliferation,invasion,and migration of colorectal cancer cells.