| Autor: |
Yihong, He, Yan, Ju, Yuzhu, Hu, Bilan, Wang, Siyao, Che, Yue, Jian, Weiling, Zhuo, Xianghui, Fu, Yongzhong, Cheng, Songping, Zheng, Ning, Huang, Zhiyong, Qian, Jiagang, Liu, Peizhi, Zhou, Xiang, Gao |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Journal of Controlled Release. 354:155-166 |
| ISSN: |
0168-3659 |
| Popis: |
Bromodomain-Containing Protein 4 (BRD4) is a member of the BET family of bromodomains, which participates in gene transcription process and is closely related to tumor progression. We observed the up-regulated expression of BRD4 in colorectal cancer (CRC) after doxorubicin (DOX) treatment, which might be a potential mechanism for DOX resistance. This study constructed the tumor-targeting (cyclo (Arg-Gly-Asp-D-Phe-Lys)-poly(ethylene glycol)-poly(ε-caprolactone)) (cRGD-PEG-PCL) copolymer for co-delivery DOX and BRD4 PROTAC degrader ARV-825 (ARV-DOX/cRGD-P) for CRC treatment. The ARV-DOX/cRGD-P complexes elicited synergistic anti-tumor effect via cell cycle arrest and the increased cell apoptosis, and mechanism studies implicated the activation of proliferation- and apoptosis-related pathways in vitro. Moreover, the administration of ARV-DOX/cRGD-P significantly improved anti-tumor activity in subcutaneous colorectal tumors and colorectal intraperitoneal disseminated tumor models in mice by promoting apoptosis, suppressing proliferation and angiogenesis of tumors. Taken together, these data reveal that ARV-825 can heighten DOX sensitivity in CRC treatment and BRD4 is a potential therapeutic target for DOX-resistant CRC. The ARV-DOX/cRGD-P preparations have outstanding anti-cancer effects and may be used for clinical treatment of colorectal cancer in the future. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect