Overexpression of CTEN is associated with gefitinib resistance in non‑small cell lung cancer

Abstract

COOH-terminus tensin-like molecule (CTEN) is a member of the tensin family, which is considered to be one of the novel proto-oncogenes involved in tumorigenesis and cancer progression. However, the mechanisms of CTEN in acquired resistance of non-small cell lung cancer (NSCLC) remain relatively unknown. The aim of the present study was to understand the roles of CTEN in acquired gefitinib resistance of NSCLC. The present study investigated the expression level of CTEN using reverse transcription-quantitative polymerase chain reaction and Western blot analysis. Cell Counting kit-8 and colony-formation assays were performed to evaluate the proliferative and colony-formative abilities of PC9 and PC9/GR cells in vitro . Mouse xenograft models were used to assess the growth of PC9/GR cells in vivo . A gefitinib-resistant NSCLC cell line (PC9/GR) was established, and the protein and mRNA expression levels of CTEN were observed to be higher in PC9/GR cells than in PC9 cells. Notably, the sensitivity of PC9/GR cells to gefitinib was observed to be decreased when CTEN was overexpressed, while PC9/GR cells with CTEN-downregulation showed markedly enhanced sensitivity to gefitinib. In vitro proliferation and colony formation assays revealed that increased CTEN markedly promoted the cell proliferative and colony-forming capacities of PC9 and PC9/GR cells, and CTEN-silencing inhibited the cell proliferative and colony-forming abilities of the PC9 and PC9/GR cells. Notably, deficient expression of CTEN notably retarded the growth of PC9/GR xenografts in vivo . In addition, the plasma mRNA expression of CTEN was notably elevated in patients with NSCLC with acquired gefitinib resistance. Overexpression of CTEN is associated with acquired gefitinib resistance in NSCLC. CTEN may be investigated as a potential therapeutic target for the treatment of patients with NSCLC with acquired gefitinib resistance.

Antagonistic Interaction between Histone Deacetylase Inhibitor: Cambinol and Cisplatin—An Isobolographic Analysis in Breast Cancer In Vitro Models

“…Our findings demonstrated that CAM inhibits cell proliferation in a dose-dependent manner in each analyzed BC cell line. These results remain in line with previously-reported findings for HCC [24], neuroblastoma [45], and multiple melanoma cell lines [46]. Our results indicate that the MCF7 luminal A cell line was the most resistant to CAM treatment, while TNBC cell lines were the most sensitive to CAM treatment.…”

“…In multiple melanoma cells, CAM inhibits cell proliferation in a time-and dosedependent manner, increasing apoptosis and arresting cells in G1 phase [46]. In our study, CAM did not significantly affect cell cycle progression; however, it slightly increased caspase-3 activation in a dose-dependent manner compared with control.…”

Identification of Gefitinib Resistance-Related lncRNA-miRNA-mRNA Regulatory Networks and Corresponding Prognostic Signature in Patients with Lung Adenocarcinoma

“…Although the initial efficacy of gefitinib is impressive, most patients eventually develop gefitinib resistance, leading to treatment failure and poor prognosis. 19 Further, the molecular mechanisms underlying gefitinib resistance in LUAD are still unclear. Thus, elucidating the underlying molecular mechanisms involved in gefitinib resistance is urgently required.…”

Mining TCGA and GEO databases for the prediction of poor prognosis in lung adenocarcinoma based on up-regulated expression of TNS4

“…[ 21 – 23 ] TNS4 mediates promoter activity in non-small cell lung cancer by inducing epithelial-mesenchymal transition and contributes to the development of resistance to tyrosine kinase inhibitors. [ 24 ] To our knowledge, the mechanism underlying the effect of TNS4 on the prognosis of LUAD has not yet been fully explored. Our bioinformatics study presented in this manuscript provides a more comprehensive prognostic analysis of LUAD.…”