Research progress on lung cancer stem cells in epidermal growth factor receptor–tyrosine kinase inhibitor targeted therapy resistance in lung adenocarcinoma

Lung cancer is the leading cause of cancer-related deaths globally.In recent years,with the widespread use of genetic testing,epidermal growth factor receptor–tyrosine kinase inhibitor(EGFR-TKI)–targeted drugs have been efficacious to patients with lung adenocarcinoma exhibiting EGFR mutations.However,resistance to treatment is inevitable and eventually leads to tumor progression,recurrence,and reduction in the overall treatment efficacy.Lung cancer stem cells play a crucial role in the development of resistance toward EGFR-TKI–targeted therapy for lung adenocarcinoma.Lung cancer stem cells possess self-renewal,multilineage differentiation,and unlimited proliferation capabilities,which efficiently contribute to tumor formation and ultimately lead to tumor recurrence andmetastasis.In this study,we evaluated the origin,markers,stemness index,relevant classic studies,resistance mechanisms,related signaling pathways,and strategies for reversing lung cancer stem cell resistance to EGFR-TKIs to provide new insights on delaying or reducing resistance and to improve the treatment efficacy of patients with EGFR-mutated lung adenocarcinoma in the future.

Effects of hypoxia inducible factor-1alpha siRNA on theinvasion of human Hela cells and expression of relatedproteins

The effects of hypoxia on the invasion and the related protein expression of Hela cells and the role of hypoxia inducible factor-1α(HIF-1α)were investigated.The Hela cells were divided into three groups,namely,H0(non-transfected Hela cells),H1(pGenesil-1 empty plasmid-transfected Hela cells),and H2(HIF-1α-shRNA plasmid-transfected Hela cells),and were cultured under hypoxia(1%O2)and normoxia for 48 h.The expression of HIF-1α,E-cadherin,β-catenin,and actin was detected using Western blot.The scratch test and the invasion assay were applied to examine the invasion in each group.The expression of HIF-1α,E-cadherin,andβ-catenin in tumor grafts was assayed immunohistochemically.Western blot results revealed that the bands of HIF-1α,E-cadherin,β-catenin,and actin proteins were detected in the H0 and H1 groups under hypoxia for 48 h.The expression of E-cadherin,β-catenin,and actin was detected in the H2 group under hypoxia for 48 h,and normoxia.In the H0,H1,and H2 groups under normoxia,and the H2 group under hypoxia for 48 h,no expression of HIF-1αwas detectable.The scratch test showed that the invasive ability in the H2 group was significantly alleviated.Immunohistochemi-cally,it was found that there was a significant difference in the expression of HIF-1α,E-cadherin,andβ-catenin between the H1 and H2 groups(P<0.05),but the difference was not significant between the H0 and H1 groups.It was concluded that the effects of hypoxia on the invasion of human cervical cancer Hela cells and the expression of related proteins(E-cadherin,β-catenin,and actin)depend on HIF-1α.