中国肿瘤生物治疗杂志2025，Vol.32Issue(1)：48-55,8.DOI:10.3872/j.issn.1007-385x.2025.01.007
PTPRD去甲基化通过PI3K/Akt/mTOR通路调控胃癌细胞的增殖、迁移及化疗耐药性
PTPRD demethylation regulates the proliferation,migration,and chemoresistance of gastric cancer cells through the PI3K/Akt/mTOR pathway
摘要
Abstract
Objective:To investigate the effect of protein tyrosine phosphatase D(PTPRD)demethylation on the proliferation,migration,and chemoresistance of gastric cancer(GC)cells through the phosphatidyl inositol 3 kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)pathway.Methods:The gastric cancer MKN-74 and MKN-45 cells,as well as human gastric mucosal epithelial GES-1 cells,GES-1 were cultured in vitro and PTPRD expression was detected.MKN-45 cells and their drug-resistant variant MKN-45/5-FU cells were routinely cultured and transfected with various vectors:PTPRD empty vector(NC group,NC/5-FU group),PTPRD overexpressing adenovirus(PTPRD group,PTPRD/5-FU group),shRNA empty vector(sh-NC group,sh-NC/5-FU group),shRNA PTPRD lentivirus(sh-PTPRD group,sh-PTPRD/5-FU group),and PTPRD overexpressing adenovirus+10 μmol/L 740Y-P treatment(PTPRD+740Y-P group,PTPRD+740Y-P/5-FU group).MTT assay and wound healing assay were used to assess cell proliferation and migration.Cell autophagy levels were assessed using autophagy assay,and the expression of epithelial-mesenchymal transition(EMT)and PI3K/Akt/mTOR pathway related proteins was detected using western blot(WB).MKN-45 cells were treated with 0,2.5,5,10,20 and 40 μmol/L 5-aza solutions,and the PTPRD mRNA expression and cell proliferation in MKN-45 cells were detected using qPCR and MTT assays.Results:PTPRD mRNA and protein were significantly downregulated in gastric cancer cells(P<0.05).Compared with the MKN-45 group,the numbers of autophagosomes and autophagosomes,as well as the protein expression of PTPRD,E-cadherin,and BAX significantly increased in the PTPRD group(all P<0.05),while cell proliferation,migration rate,and protein expression of p-PI3K,vimentin,p-Akt,and p-mTOR decreased significantly(all P<0.05);However,in the sh-PTPRD group,cell proliferation activity,migration rate,and protein expression of p-PI3K,vimentin,p-Akt,and p-mTOR increased notably,while the quantity of autophagosomes,autophagosomes,and protein expression of PTPRD,E-cadherin,and BAX decreased(all P<0.05).Compared with the PTPRD group,the PTPRD+740Y-P group showed an increase in cell proliferation activity,migration rate,protein expression of p-PI3K,vimentin,p-Akt,and p-mTOR(all P<0.05),and a decrease in number of autophagosomes,autophagosomes,and protein expression of PTPRD,E-cadherin,and BAX(all P<0.05).With the increase of 5-aza concentration,the mRNA expression of PTPRD in MKN-45 cells increased(P<0.05),while the cell proliferation activity decreased(P<0.05).Compared with the MKN-45/5-FU group,the cell migration rate and proliferation activity decreased in PTPRD/5-FU group,while the sh-PTPRD/5-FU group showed an increase in cell migration rate and proliferation activity(all P<0.05).Compared with the PTPRD/5-FU group,the PTPRD+740Y-P/5-FU group showed an increase in cell migration rate and proliferation activity(all P<0.05).Conclusion:PTPRD is downregulated in GC cells,and its demethylation may inhibit proliferation and migration of GC cells and enhance chemosensitivity by suppressing the PI3K/Akt/mTOR pathway.关键词
蛋白酪氨酸磷酸酶D/胃癌/增殖/迁移/PI3K/Akt/mTOR通路/化疗耐药性/甲基化Key words
protein tyrosine phosphatase D(PTPRD)/gastric cancer(GC)/proliferation/migration/PI3K/Akt/mTOR pathway/chemotherapy resistance/methylation分类
临床医学引用本文复制引用
刘妍慧,高紫玉,任鹏,杜予馨,刘彩霞,邢智伟..PTPRD去甲基化通过PI3K/Akt/mTOR通路调控胃癌细胞的增殖、迁移及化疗耐药性[J].中国肿瘤生物治疗杂志,2025,32(1):48-55,8.基金项目
内蒙古自治区科技计划项目(No.2020GG0171) （No.2020GG0171）
内蒙古自治区高等学校科学研究项目(No.NJZZ23013) （No.NJZZ23013）
