高级检索
当前位置: 首页 > 详情页

Inhibition of BRD4 enhanced the tumor suppression effect of dasatinib in gastric cancer

文献详情

资源类型:
WOS体系:
Pubmed体系:

收录情况: ◇ SCIE

机构: [1]Navy Mil Med Univ, Fac Naval Med, Dept Navy Environm & Occupat Hlth, Shanghai, Peoples R China [2]Yunnan Univ, Sch Med, Kunming, Yunnan, Peoples R China [3]Kunming Univ Sci & Technol, Affiliated Hosp, Peoples Hosp Yunnan Prov 1, Dept Med Oncol, Kunming, Yunnan, Peoples R China
出处:
ISSN:

关键词: Gastric cancer BRD4 Molibresib Dasatinib Prognosis Targeted therapy

摘要:
BRD4, a member of the bromodomain and extraterminal (BET) family, is elevated in multiple cancer tissues, including gastric cancer (GC). Targeted therapy with BRD4 may help improve the overall survival of patients with GC. Meanwhile, the approved multi-target kinase inhibitor, dasatinib, was recently reported to show varied tumor-suppressive effects in GC cells. This study investigated BRD4 expression in vivo and in vitro using immunohistochemistry and western blotting, respectively. We discussed the relationship between BRD4 expression and patient prognosis. Next, the antitumor efficacy of dasatinib was measured in BRD4-knockdown GC cells to determine the role of BRD4 blockage in dasatinib treatment. Finally, molibresib, a BET inhibitor, was used to measure the cooperative function of BRD4 inhibition and dasatinib treatment in three GC cell lines. Epithelial BRD4 expression was higher in tumoral and metastatic tissues and was strongly associated with unfavorable tumor, node, and metastasis stages and survival. BRD4 expression was heterogeneous in the three GC cell lines tested in vitro. In SGC7901, a BRD4-high GC cell line, knockdown of BRD4 using specific siRNAs suppressed cell growth individually and cooperatively with dasatinib. Moreover, molibresib and dasatinib showed a cooperative effect in suppressing the proliferation of BRD4-high GC cells. In conclusion, we confirmed that increased epithelial BRD4 expression is associated with poor disease stage and prognosis in GC and BRD4 blockage might be a valuable strategy to improve the sensitivity of dasatinib and other drugs in the chemotherapy of advanced GC.

基金:
语种:
被引次数:
WOS:
PubmedID:
中科院(CAS)分区:
出版当年[2022]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
最新[2023]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
JCR分区:
出版当年[2021]版:
Q3 ONCOLOGY
最新[2023]版:
Q2 ONCOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者:
第一作者机构: [1]Navy Mil Med Univ, Fac Naval Med, Dept Navy Environm & Occupat Hlth, Shanghai, Peoples R China [2]Yunnan Univ, Sch Med, Kunming, Yunnan, Peoples R China
共同第一作者:
通讯作者:
推荐引用方式(GB/T 7714):
APA:
MLA:

资源点击量:82478 今日访问量:0 总访问量:681 更新日期:2025-01-01 建议使用谷歌、火狐浏览器 常见问题

版权所有©2020 云南省第一人民医院 技术支持:重庆聚合科技有限公司 地址:云南省昆明市西山区金碧路157号