Autor: |
Ruoqin Wang, Linqing Sun, Suhua Xia, Hongya Wu, Yanchao Ma, Shenghua Zhan, Guangbo Zhang, Xueguang Zhang, Tongguo Shi, Weichang Chen |
Jazyk: |
angličtina |
Rok vydání: |
2021 |
Předmět: |
|
Zdroj: |
Cell Death and Disease, Vol 12, Iss 5, Pp 1-17 (2021) |
Druh dokumentu: |
article |
ISSN: |
2041-4889 |
DOI: |
10.1038/s41419-021-03736-2 |
Popis: |
Abstract Emerging evidence suggests that cellular senescence induced by chemotherapy has been recognized as a new weapon for cancer therapy. This study aimed to research novel functions of B7-H3 in cellular senescence induced by a low dose of doxorubicin (DOX) in colorectal cancer (CRC). Here, our results demonstrated that B7-H3 knockdown promoted, while B7-H3 overexpression inhibited, DOX-induced cellular senescence. B7-H3 knockdown dramatically enhanced the growth arrest of CRC cells after low-dose DOX treatment, but B7-H3 overexpression had the opposite effect. By RNA-seq analysis and western blot, we showed that B7-H3 prevented cellular senescence and growth arrest through the AKT/TM4SF1/SIRT1 pathway. Blocking the AKT/TM4SF1/SIRT1 pathway dramatically reversed B7-H3-induced resistance to cellular senescence. More importantly, B7-H3 inhibited DOX-induced cellular senescence of CRC cells in vivo. Therefore, targeting B7-H3 or the B7-H3/AKT/TM4SF1/SIRT1 pathway might be a new strategy for promoting cellular senescence-like growth arrest during drug treatment in CRC. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
|