Novel Mitochondria-Based Targeting Restores Responsiveness in Therapeutically Resistant Human Lung Cancer Cells.
Mol Cancer Ther
; 20(12): 2527-2538, 2021 12.
Article
em En
| MEDLINE
| ID: mdl-34583981
ABSTRACT
Cisplatin and tyrosine kinase inhibitors (TKI) are recommended to treat non-small cell lung cancer (NSCLC). However, ubiquitously acquired drug resistance in patients with NSCLC diminishes their therapeutic efficacy. Strategies for overcoming cisplatin and TKI resistance are an unmet medical need. We previously described a group of near-infrared heptamethine carbocyanine fluorescent dyes, referred to as DZ, with tumor-homing properties via differentially expressed organic anion-transporting polypeptides on cancer cells. This group of organic dyes can deliver therapeutic payloads specifically to tumor cells in the form of a chemical conjugate. We synthesized DZ-simvastatin (DZ-SIM) initially to target cholesterol biosynthesis in lung cancer cells. DZ-SIM killed both cisplatin-sensitive and cisplatin-resistant as well as EGFR-TKI-sensitive and EGFR-TKI-resistant lung cancer cells. This conjugate specifically accumulated in and effectively inhibited the growth of xenograft tumors formed by NSCLC cells resistant to first-generation (H1650) and third-generation (PC9AR) EGFR TKIs. DZ-SIM induced cell death by targeting mitochondrial structure and function. We concluded that DZ-SIM could be a promising novel therapy for overcoming drug resistance in patients with NSCLC.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Pulmonar de Células não Pequenas
/
Resistencia a Medicamentos Antineoplásicos
/
Neoplasias Pulmonares
/
Mitocôndrias
Limite:
Humans
Idioma:
En
Revista:
Mol Cancer Ther
Assunto da revista:
ANTINEOPLASICOS
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China