The Effect of IkappaBalpha-SR Gene Transfer on the Sensitivity of Human Lung Cancer Cell Lines to Cisplation and Paclitaxel / 결핵
Tuberculosis and Respiratory Diseases
; : 122-134, 2001.
Article
en Ko
| WPRIM
| ID: wpr-36115
Biblioteca responsable:
WPRO
ABSTRACT
BACKGROUND: Some chemotherapeutic drugs induce NF-κB activation by degrading the IκBα protein in cancer cells which contributes to anticancer drug resistance. We hypothesized that inhibiting IκBα degradation would block NF-κB activation and result in increased tumor cell mortality in response to chemotherapy. METHODS: The "superrepressor" form of the NF-κB inhibitor was transferred by an adenoviral vector (Ad-IκBα-SR) to the human lung cancer cell lines (NCI H157 and NCI H460). With a MTT assay, the level of sensitization to cisplatin and paclitaxel were measured. To confirm the mechanism, an EMSA and Annexin V assay were performed. RESULTS: EMSA showed that IκBα-SR effectively blocked the NF-κB activation induced by cisplatin. Transduction with Ad-IκBα-SR resulted in an increased sensitivity of the lung cancer cell lines to cisplatin and paclitaxel by a factor of 2~3 in terms of IC50. Annexin-V analysis suggests that this increment in chemosensitivity to cisplatin probably occurs through the induction of apoptosis. CONCLUSION: The blockade of chemotherapeutics induced NF-κB activation by inducing Ad-IκBα-SR, increased apoptosis and increasing the chemosensitivity of the lung cancer cell lines tested, subsequently. Gene transfer of IκBα-SR appears to be a new therapeutic strategy of chemosensitization in lung cancer.
Palabras clave
Texto completo:
1
Índice:
WPRIM
Asunto principal:
Resistencia a Medicamentos
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Línea Celular
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Adenoviridae
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Mortalidad
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Cisplatino
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Paclitaxel
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Apoptosis
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Anexina A5
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Concentración 50 Inhibidora
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Quimioterapia
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
Ko
Revista:
Tuberculosis and Respiratory Diseases
Año:
2001
Tipo del documento:
Article