骨肉瘤
癌症研究
细胞生长
细胞凋亡
MAPK/ERK通路
蛋白激酶B
转移
车站3
血小板源性生长因子受体
体内
细胞周期
医学
信号转导
化学
生物
内科学
癌症
受体
生长因子
细胞生物学
生物技术
生物化学
作者
Yinda Qiu,Hao Yan,Ruiling Zheng,Xiaojing Chen,Yi Wang,Yan Qi,Yanfei Ye,Jianxia Zhang,Haoyi Han,Kun Wang,Yunjie Zhao,Lehao Huang,Xiaokun Li,Zhiguo Liu
标识
DOI:10.1016/j.cbi.2022.110200
摘要
Osteosarcoma (OS) is a group of malignant tumors with high rates of malignancy and metastasis. OS most commonly affects adolescents and young individuals. However, owing to the lack of effective targeted treatments, the 5-year survival rate for OS is still around 20%. Thus, it is essential to develop effective drugs with low toxicity for OS treatment. In the present study, we investigated the antitumor effect and underlying mechanism of cyy260 in OS via suppressing PDGFR-β and its downstream pathway. We demonstrated that cyy260 inhibits OS cell proliferation and promotes apoptosis via inducing DNA damage and causing cell cycle arrest. More importantly, cyy260 also significantly inhibits tumor migration. Further analysis of molecular mechanisms confirmed that PDGFR-β and its downstream AKT, STAT3, and ERK were involved in the cyy260-mediated antitumor effect. Analysis of subcutaneously transplanted tumors in mice showed that cyy260 suppressed tumor cell growth and exhibited low toxicity in vivo. Collectively, these findings proved that cyy260 could serve as a promising PDGFR-β inhibitor for the treatment of OS.
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