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Relationship between long non-coding RNA PCAT-1 expression and gefitinib resistance in non-small-cell lung cancer cells.
- Source :
-
Respiratory research [Respir Res] 2021 May 12; Vol. 22 (1), pp. 146. Date of Electronic Publication: 2021 May 12. - Publication Year :
- 2021
-
Abstract
- Background: Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has been used as first-line treatment for advanced non-small-cell lung cancer (NSCLC). However, during treatment, cancer cells often develop resistance to gefitinib, the mechanisms of which are not fully understood. This study was designed to elucidate the expression and role of long non-coding RNA (lncRNA)-PCAT-1, a potential biomarker for drug resistance and a therapeutic target for NSCLC, in gefitinib resistance in NSCLC cells.<br />Methods: In this study, we verified differential PCAT-1 expression in NSCLC gefitinib-resistant tissues or cells. PCAT-1 knockdown, clone formation, Transwell, flow cytometry, and immunofluorescence assays were used to verify the correlation between PCAT-1 and gefitinib sensitivity. A nude mouse tumor-bearing model verified that PCAT-1 can reverse gefitinib resistance in vivo. Then, a PI3K/Akt agonist was used to verify the possible mechanism of PCAT-1 action.<br />Results: PCAT-1 is highly expressed in gefitinib-resistant NSCLC tissues and cells. PCAT-1 knockdown enhanced gefitinib sensitivity and gefitinib-induced apoptosis in H1299/GR cells. PCAT-1 knockdown reduced tumor volume and weight, and reversed acquired gefitinib resistance in vivo. PCAT-1 knockdown inhibited AKT and GSK3 phosphorylation in H1299/GR cells. A PI3K/AKT agonist reversed PCAT-1 knockdown-mediated enhancement of gefitinib sensitivity in H1299/GR cells CONCLUSION: PCAT-1 knockdown improves sensitivity to gefitinib by inhibition of AKT and GSK3 phosphorylation in NSCLC. PCAT-1 is as potential target for improving the clinical efficacy of gefitinib.
- Subjects :
- Animals
Apoptosis drug effects
Carcinoma, Non-Small-Cell Lung genetics
Carcinoma, Non-Small-Cell Lung metabolism
Carcinoma, Non-Small-Cell Lung pathology
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Glycogen Synthase Kinase 3 metabolism
Humans
Lung Neoplasms genetics
Lung Neoplasms metabolism
Lung Neoplasms pathology
Male
Mice, Nude
Phosphatidylinositol 3-Kinase metabolism
Phosphorylation
Proto-Oncogene Proteins c-akt metabolism
RNA, Long Noncoding genetics
Signal Transduction
Xenograft Model Antitumor Assays
Mice
Antineoplastic Agents pharmacology
Carcinoma, Non-Small-Cell Lung drug therapy
Drug Resistance, Neoplasm
Gefitinib pharmacology
Lung Neoplasms drug therapy
Protein Kinase Inhibitors pharmacology
RNA, Long Noncoding metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1465-993X
- Volume :
- 22
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Respiratory research
- Publication Type :
- Academic Journal
- Accession number :
- 33980216
- Full Text :
- https://doi.org/10.1186/s12931-021-01719-7