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1.
Respir Res ; 22(1): 146, 2021 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-33980216

RESUMEN

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. 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. 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.


Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Resistencia a Antineoplásicos , Gefitinib/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , ARN Largo no Codificante/metabolismo , Animales , Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Glucógeno Sintasa Quinasa 3/metabolismo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Ratones Desnudos , Fosfatidilinositol 3-Quinasa/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Largo no Codificante/genética , Transducción de Señal , Ensayos Antitumor por Modelo de Xenoinjerto
2.
Transl Cancer Res ; 11(12): 4349-4358, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36644184

RESUMEN

Background: A lung cancer screening project was conducted by attracting active participation to evaluate its feasibility and effectiveness in areas with poor basic medical education. Methods: This project entailed a prospective, single-arm study which was conducted by means of delivering a lecture on lung cancer at the Honghe Lung Cancer Medical Center to attract public attention and attendance from 28 November 2020 to 21 December 2021. A questionnaire comprising 7 high-risk factors was completed by participants to identify high-risk individuals for further chest low-dose computed tomography examination. Non calcified nodules with a diameter ≥5 mm were deemed positive nodules. The positive nodules were discussed by a multidisciplinary team and treatment suggestions were given. Finally, we analyzed participant information, examination adherence, lung cancer detection rate, and staging. Results: A total of 6,121 individuals were attracted to the project, and 5,925 (96.8%) agreed to participate. Of these, 5,889 (99.4%) completed the survey, with 4,627 (78.6%) in the high-risk group and 1,262 (21.4%) in the non-high-risk group. The proportion of males in the high-risk group was higher than that in the non-high-risk group, and the difference was statistically significant among those aged 40-49 years, 50-59, years and 60-69 years; P<0.01. In the high-risk population, 4,536 (98.0%) of participants adhered to examination, among whom 2,007 (44.2%) with positive nodules, 1,220 (26.9%) with negative nodules, and 1,309 (28.9%) without nodules showed statistical differences in age; P<0.01. The detection rate of lung cancer was 2.2% (99/4,536); 94.0% (93/99) of whom were stage 0-I patients. Conclusions: A health lecture-based approach to improving public participation in regions with poor health education is likely to be effective in promoting the early detection of lung cancer.

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