HKB99,an allosteric inhibitor of phosphoglycerate mutase 1,suppresses invasive pseudopodia formation and upregulates plasminogen activator inhibitor-2 in erlotinib-resistant non-small cell lung cancer cells

• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2021,（1）
• 所属期刊栏目: Chemotherapy
• 页码范围: 115-119
• 页数: 5页
• 语种: 英文

摘要

Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs),such as erlotinib,remains a major challenge in the targeted therapy of non-small cell lung cancer(NSCLC).HKB99 is a novel allosteric inhibitor of phosphoglycerate mutase 1(PGAM1)that preferentially suppresses cell proliferation and induces more apoptosis in acquired erlotinib-resistant HCC827ER cells compared with its parental HCC827 cells.In this study we identified the molecular biomarkers for HKB99 response in erlotinib-resistant HCC827ER cells.We showed that HCC827ER cells displayed enhanced invasive pseudopodia structures as well as downregulated plasminogen activator inhibitor-2(PAI-2).Meanwhile,PAI-2 knockdown by siPAI-2 candidates decreased the sensitivity of HCC827 parental cells to erlotinib.Moreover,HKB99(5 μM)preferentially inhibited the invasive pseudopodia formation and increased the level of PAf-2 in HCC827ER cells.Collectively,this study provides new insight into the role of PAI-2 in regulating the sensitivity of erlotinib resistant NSCLC cells to PGAM1 inhibitor.Furthermore,PAI-2 level might be considered as a potential biomarker for predicting the efficacy of the PGAM1 allosteric inhibitor on the erlotinib resistant NSCLC cells.