Effects of the MAPK/p38/JNK/ERK signaling pathway on the migration and adhesion of hepatocellular carcinoma cells
XU Rui
ZHANG Yan
LI Na
Abstract：Objective To investigate the effect of the mitogen-activated protein kinase(MAPK)/p38/c-Jun N-terminal Kinase(JNK)/extracellular signal-regulated kinase(ERK)signaling pathway on the migration and adhesion of hepatocellular carcinoma(HCC)cells.Methods From January 2020 to January 2021,HCC and paracancerous specimens from 50 HCC patients underwent surgical resection in the Department of Hepatobiliary Surgery of our hospital were selected for immunohistochemical detection of positive expressions of p38 MAPK,JNK and ERK1.HepG2 cells were induced with blank control,0.1％DMSO,10 μL of anisomycin(p38 MAPK agonist),10 μL of SP600125(JNK inhibitor)and 10 μL of PD98059(ERK1/2 inhibitor).After 24 h of cell culture,polymerase chain reaction(PCR)was performed to detect the mRNA levels of p38 MAPK,JNK and ERK1.Migratory distance was measured by wound healing assay.The number of adhesive cells was counted by fluorescence staining.Protein levels of MMP-9 and E-cadherin were detected by Western blot.Results The positive expression rates of p38 MAPK,JNK and ERK1 in 50 HCC patients were 32％(16/50),62％(31/50)and 88％(44/50),respectively(x2=22.920,P＜0.001).The positive expression rates of p38 MAPK,JNK and ERK1 in paracancerous tissues of 50 HCC patients were 79％(39/50),4％(2/50)and 38％(19/50),respectively(x2=57.170,P＜0.001).Compared with DMSO-induced cells,the mRNA level of p38 MAPK was significantly upregulated in cells induced with anisomycin,SP600125 and PD98059,but the mRNA levels of JNK and ERK1 were significantly downregulated(P＜0.05).There were no significant differences in the migration distance and number of adhesive cells between those induced with blank control versus DMSO(P＞0.05).In comparison to DMSO-induced cells,cells induced with anisomycin,SP600125 and PD98059 had significantly shorter migration distance,less number of adhesive cells,lower protein level of MMP-9 and higher protein level of E-cadherin(P＜0.05).Conclusion The positive expressions of JNK and ERK1 increase,while the positive expression of p38 MAPK decrease in HCC tissues.Treatment of JNK inhibitors,ERK1 inhibitors and p38 MAPK agonists can significantly inhibit the migration and adhesion of HCC cells by downregulating MMP-9 and E-cadherin.
Keywords：liver cancermitogen-activated protein kinasec-Jun N-terminal Kinaseextracellular signal-regulated kinase
Publication Date：2025-10-26
Online Publishing Date：2025-11-19(First online date of this platform, not the publication date of the document)
Pages：6( 1600-1604,1610 )