Calpain 2 knockdown promotes cell apoptosis and restores gefitinib sensitivity through epidermal growth factor receptor/protein kinase B/survivin signaling.
Oncol Rep
; 40(4): 1937-1946, 2018 Oct.
Article
em En
| MEDLINE
| ID: mdl-30106446
ABSTRACT
Gefitinib, an epidermal growth factor receptor (EGFR)specific drug, is effective for ~1 year, after which resistance is inevitable. Calpain 2 (CAPN2) is known to serve a role in the drug response and resistance in certain cancer therapies. However, the full function of CAPN2, particularly in nonsmall cell lung cancer, has not yet been elucidated. In the present study, CAPN2 expression in gefitinibresistant lung adenocarcinoma cells was investigated. CAPN2 function in these cells was further evaluated using gene knockdown both in vitro and in vivo. The results demonstrated that CAPN2 was strongly associated with gefitinibresistance, and CAPN2 mRNA and protein expression levels were significantly increased in gefitinibresistant cell lines. Furthermore, CAPN2 knockdown inhibited gefitinibresistant cell proliferation in vitro and in vivo. CAPN2 conferred gefitinibresistance by inhibiting cell apoptosis and arresting the cell cycle. CAPN2 knockdown also induced caspase activation and mitochondrial dysfunction, and its function in gefitinib resistance appeared to be largely mediated by EGFR/protein kinase B/survivin signaling pathway activation. These results suggest that CAPN2 is responsible for EGFRtyrosine kinase inhibitor resistance, and CAPN2 inhibition may be used to provide therapeutic benefits in the treatment of gefitinib resistance.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
/
Calpaína
/
Apoptose
/
Carcinoma Pulmonar de Células não Pequenas
/
Resistencia a Medicamentos Antineoplásicos
/
Proteínas Proto-Oncogênicas c-akt
/
Proteínas Inibidoras de Apoptose
/
Receptores ErbB
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Oncol Rep
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2018
Tipo de documento:
Article