Silencing STAT3 enhances sensitivity of cancer cells to doxorubicin and inhibits tumor progression.
Life Sci
; 275: 119369, 2021 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-33745894
ABSTRACT
AIMS:
Despite extensive efforts to find new treatments, chemotherapy is still one of the first and foremost choices for cancer treatment. The main problems of using these drugs are the resistance of cancer cells and reducing their sensitivity to chemotherapy as well as the side effects of their systemic administration. Because STAT3 plays a very important role in the survival and susceptibility of cancer cells to apoptosis, we hypothesized that suppression of STAT3 expression could induce greater susceptibility to DOX-induced cancer cell death. MATERIALS ANDMETHODS:
We used pegylated chitosan lactate nanoparticles (NPs) functionalized by TAT peptide and folate to deliver STAT3 siRNA and DOX to cancer cells simultaneously, both in vitro and in vivo. KEYFINDINGS:
The results showed that NPs could effectively deliver siRNA and DOX to cancer cells, which was associated with suppression of STAT3 expression and increased induction of DOX-mediated cell death. Concomitant delivery of DOX and STAT3 siRNA also suppressed tumor growth in 4T1 and CT26 cancer models, which was associated with induction of anti-tumor immune responses.SIGNIFICANCE:
These findings suggest that the use of NPs can be an effective strategy for the targeted delivery of STAT3-specific siRNA/DOX to cancer cells.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doxorrubicina
/
Inativação Gênica
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Fator de Transcrição STAT3
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Antibióticos Antineoplásicos
/
Neoplasias
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article