机构：[1]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Guoxue Xiang 37, Chengdu 610041, China四川大学华西医院[2]Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA[3]School of Automation Science and Electrical Engineering, Beihang University, Beijing, 100083, China[4]Department of Plastic Surgery, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China[5]Vaccine and Immunotherapy Center, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA[6]Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA[7]Diagnostic Radiology & Nuclear Medicine, University of Maryland School of Medicine, 670 W. Baltimore Street, Baltimore,MD 21201, USA[8]Department of Pediatric Surgery, West China Hospital, Sichuan University, Guoxue Xiang 37, Chengdu 610041, China四川大学华西医院
Castration-resistant prostate cancer (CRPC) is the most common cause of death in men. The effectiveness of HDAC inhibitors has been demonstrated by preclinical models, but not in clinical studies, probably due to the ineffectively accumulation of HDACI in prostate cancer cells. The purpose of this work was to evaluate effects of a novel HDACI (CN133) on CRPC xenograft model and 22Rv1 cells, and develops methods, PET/CT imaging, to detect the therapeutic effects of CN133 on this cancer.
We designed and performed study to compare the effects of CN133 with SAHA on the 22Rv1 xenograft model and 22Rv1 cells. Using PET/CT imaging with [11C] Martinostat and [18F] FDG, we imaged mice bearing 22Rv1 xenografts before and after 21-day treatment with placebo and CN133 (1 mg/kg), and uptake on pre-treatment and post-treatment imaging was measured. The anti-tumor mechanisms of CN133 were investigated by qPCR, western blot, and ChIP-qPCR.
Our data showed that the CN133 treatment led to a 50% reduction of tumor volume compared to the placebo that was more efficacious than SAHA treatment in this preclinical model. [11C] Martinostat PET imaging could identify early lesions of prostate cancer and can also be used to monitor the therapeutic effect of CN133 in CRPC. Using pharmacological approaches, we demonstrated that effects of CN133 showed almost 100-fold efficacy than SAHA treatment in the experiment of cell proliferation, invasion, and migration. The anti-tumor mechanisms of CN133 were due to the inhibition of AR signaling pathway activity by decreased HDAC 2 and 3 protein expressions.
Taken together, these studies provide not only a novel epigenetic approach for prostate cancer therapy but also offering a potential tool, [11C] Martinostat PET/CT imaging, to detect the early phase of prostate cancer and monitor therapeutic effect of CN133. These results will likely lead to human trials in the future.
基金：
This work was supported by a pilot funding from the
Athinoula A. Martinos Center for Biomedical Imaging at the
Massachusetts General Hospital (C.W.), and a short-term visiting program
of Sichuan University (Z.C.).
语种：
外文
PubmedID：
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出版当年[2021]版：
大类|1 区医学
小类|1 区核医学
最新[2023]版：
大类|1 区医学
小类|1 区核医学
第一作者：
第一作者机构：[1]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Guoxue Xiang 37, Chengdu 610041, China[2]Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
通讯作者：
推荐引用方式(GB/T 7714)：
Zude Chen,Xiashuang Wang,Xiaoshuang Yang,et al.Imaging assisted evaluation of antitumor efficacy of a new histone deacetylase inhibitor in the castration-resistant prostate cancer.[J].European journal of nuclear medicine and molecular imaging.2021,48(1):53-66.doi:10.1007/s00259-020-04896-7.
APA：
Zude Chen,Xiashuang Wang,Xiaoshuang Yang,Yulong Xu,Yu Yang...&Changning Wang.(2021).Imaging assisted evaluation of antitumor efficacy of a new histone deacetylase inhibitor in the castration-resistant prostate cancer..European journal of nuclear medicine and molecular imaging,48,(1)
MLA：
Zude Chen,et al."Imaging assisted evaluation of antitumor efficacy of a new histone deacetylase inhibitor in the castration-resistant prostate cancer.".European journal of nuclear medicine and molecular imaging 48..1(2021):53-66
医学