Effects of Nivolumab and Ipilimumab on the suppression of cisplatin resistant small cell lung cancer cells.
Invest New Drugs
; 40(4): 709-717, 2022 08.
Article
em En
| MEDLINE
| ID: mdl-35438354
ABSTRACT
BACKGROUND:
Small cell lung cancer (SCLC) accounts for nearly 10-15% of all lung cancer cases. Although many chemotherapy drugs, such as cisplatin and etoposide, were approved as primary therapy for SCLC patients, the prognosis is poor. In this study, we aimed to explore novel therapeutic strategy against SCLC.METHODS:
Two SCLC cell lines, LTEP-P and LTEP-P/DDP1.0, were treated with cisplatin, in the absence or presence of Nivolumab + Ipilimumab combination, and the cell viability was measured. Tumor size and mouse survival rate were examined upon different drug treatments. Protein levels of PD-1 and CTLA4 were detected in normal and SCLC cells by Western blot. Cellular cytotoxicity induced by T lymphocytes was measured by thymidine incorporation assay. Tumor infiltrated T cell populations from LTEP-P and LTEP/DDP1.0 tumor-bearing mice were analyzed by flow cytometry.RESULTS:
LTEP-P cells, but not LTEP/DDP1.0 cells, exhibited decreased cell viability upon cisplatin, Nivolumab and Ipilimumab combinational treatment. T lymphocytes significantly inhibited the growth of LTEP-P cells in the presence of nivolumab and ipilimumab. The combinational therapy improved survival rate and inhibited tumor growth in LTEP-P tumor-bearing mice, but showed no effect on LTEP/DDP1.0 tumor-bearing mice. Nivolumab and Ipilimumab synergized with cisplatin in increasing CD8 + and CD4 + T cell population, while decreasing Treg population in LTEP-P tumor-bearing mice.CONCLUSIONS:
The combinational therapy by cisplatin, Nivolumab and Ipilimumab could be an effective strategy against LTEP-P cells, accompanied with increased cytotoxic T cell populations, but has no significant effect against DDP-resistant lung adenocarcinoma cells.Palavras-chave
Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Pequenas Células do Pulmão
/
Neoplasias Pulmonares
Limite:
Animals
Idioma:
En
Revista:
Invest New Drugs
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China