辐射敏感性
癌症研究
细胞凋亡
克隆形成试验
胰腺癌
细胞周期
放射增敏剂
化学
Ku70型
分子生物学
生物
DNA修复
癌症
医学
内科学
放射治疗
基因
生物化学
遗传学
作者
Zhibing Wu,Saisai Jing,Yanhong Li,Yuting Gao,Shuhuan Yu,Zhitian Li,Yanyan Zhao,Ji-Gang Piao,Shenglin Ma,Xufeng Chen
标识
DOI:10.1016/j.biopha.2017.02.067
摘要
Suberoyl anilide hydroxamic acid (SAHA) is one of the most promising Histone deacetylases(HDAC) inhibitors which has shown significant anti-tumor activity for many malignancies. We explored the potential mechanism of the radiosensitivity effect of SAHA in Panc-1 cells and attempted to develop SAHA as a systemic treatment strategy for pancreatic cancer. Growth inhibition was detected by CCK-8 assay. Radiosensitizing enhancement ratio was determined by clonogenic assay. The cell cycle and apoptosis assay was detected using flow cytometry and annexin-V/PI. The level of Bax, Bcl-2, Ku70, Ku86, RAD51, RAD54 protein expression were detected using Western blot analysis. Gene silencing was processed by lentiviral vector and qRT-PCR was performed to detect mRNA expression. The results revealed that SAHA inhibited the proliferation of Panc-1 cells. SAHA enhanced the radiosensitivity with a sensitization enhancement ratio(SER) of 1.10 of the Panc-1 cells. SAHA induced G2-M phase arrest and apoptosis of Panc-1 cells with radiation. SAHA upregulated Bax and downregulated Bcl-2, Ku70, Ku86, RAD51, RAD54 protein expression of irradiated Panc-1 cells. SAHA enhanced the radiosensitivity of Panc-1 cells by modulating RAD51 expression. SAHA enhanced radiosensitivity to pancreatic carcinoma Panc-1 cells. It was associated with the G2-M phase arrest and apoptosis via modulation of Bax and Bcl-2 expression. Downregulation of Ku70, Ku86, RAD51 and RAD54 expression caused suppression of HR-mediated DNA repair. SAHA is a good radiosensitizer for pancreatic cancer treatment.
科研通智能强力驱动
Strongly Powered by AbleSci AI