Triptolide enhances chemotherapeutic efficacy of antitumor drugs in non-small-cell lung cancer cells by inhibiting Nrf2-ARE activity.
Toxicol Appl Pharmacol
; 358: 1-9, 2018 11 01.
Article
em En
| MEDLINE
| ID: mdl-30196066
ABSTRACT
Non-small cell lung cancer (NSCLC) has a high mortality rate worldwide. Various treatments strategies have been used against NSCLC including individualized chemotherapies, but innate or acquired cancer cell drug resistance remains a major obstacle. Recent studies revealed that the Kelch-like ECH associated protein 1/Nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2) pathway is intimately involved in cancer progression and chemoresistance. Thus, antagonizing Nrf2 would seem to be a viable strategy in cancer therapy. In the present study a traditional Chinese medicine, triptolide, was identified that markedly inhibited expression and transcriptional activity of Nrf2 in various cancer cells, including NSCLC and liver cancer cells. Consequently, triptolide made cancer cells more chemosensitivity toward antitumor drugs both in vitro and in a xenograft tumor model system using lung carcinoma cells. These results suggest that triptolide blocks chemoresistance in cancer cells by targeting the Nrf2 pathway. Triptolide should be further investigated in clinical cancer trials.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fenantrenos
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Carcinoma Pulmonar de Células não Pequenas
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Antineoplásicos Alquilantes
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Diterpenos
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Fator 2 Relacionado a NF-E2
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Elementos de Resposta Antioxidante
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Neoplasias Pulmonares
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China