Lang J.,Huazhong University of Science and Technology |
Lang J.,Hubei Province Key Laboratory of Molecular Imaging |
Lang J.,Fudan University |
Lan X.,Huazhong University of Science and Technology |
And 13 more authors.
Nuclear Medicine and Biology | Year: 2015
Introduction: Cancer stem cells (CSCs) are a subpopulation within a tumor, which possesses the characteristics of self-renewal, differentiation, tumorigenicity, and drug resistance. The aim of this study was to target the colorectal CSC marker CD133 with an131I-labeled specific monoclonal antibody (AC133 mAb) in a nude mouse xenograft model. Methods: Colorectal adenocarcinoma cells (LoVo cell line) were separated into CD133(+) and CD133(-) cells by magnetic activated cell sorting. CD133(+), CD133(-), and unsorted LoVo cells were cultured and then implanted subcutaneously into the lower limbs of nude mice (n=5). AC133 mAb was labeled with 131I by the iodogen method. Results: The radiolabeled compound, 131I-AC133 mAb, showed high stability, specificity, and immunoactivity in vitro. Obvious accumulation of 131I-AC133 mAb was seen in nude mice bearing xenografts of CD133(+) and unsorted LoVo cells, but no uptake was found in mice bearing CD133(-) xenografts or specifically blocked xenografts. Biodistribution analysis showed that the tumor uptake of 131I-AC133 mAb was 6.97±1.40, 1.35±0.48, 6.12±1.91, and 1.61±0.44% ID/g (n=4) at day 7 after injection of 131I-AC133 mAb in CD133(+), CD133(-), unsorted LoVo cell and specifically blocked xenografts, respectively. The results of immunofluorescence, autoradiography, and western blotting further verified the specific binding of 131I-AC133 mAb to CD133(+) tumors. Conclusions: This study demonstrates the possibility of targeting CSCs with a radiolabeled AC133 mAb in colorectal cancer xenografts based on in vitro, ex vivo, and in vivo experiments. Our findings suggest a new method for imaging CSCs non-invasively. © 2015 Elsevier Inc. Source
Gao X.,Huazhong University of Science and Technology |
Gao X.,Hubei Province Key Laboratory of Molecular Imaging |
Wu X.,Huazhong University of Science and Technology |
Zhang X.,Huazhong University of Science and Technology |
And 8 more authors.
Biochemical and Biophysical Research Communications | Year: 2016
Thyroid cancer is a common malignancy of the endocrine system. Although radioiodine 131I treatment on differentiated thyroid cancer is widely used, many patients still fail to benefit from 131I therapy. Therefore, exploration of novel targeted therapies to suppress tumor growth and improve radioiodine uptake remains necessary. Bromodomain-containing protein 4 (BRD4) is an important member of the bromodomain and extra terminal domain family that influences transcription of downstream genes by binding to acetylated histones. In the present study, we found that BRD4 was up-regulated in thyroid cancer tissues and cell lines. Inhibition of BRD4 in thyroid cancer cells by JQ1 resulted in cell cycle arrest at G0/G1 phase and enhanced 131I uptake in vitro and suppressed tumor growth in vivo. Moreover, JQ1 treatment suppressed C-MYC but enhanced NIS expression. We further demonstrated that BRD4 was enriched in the promoter region of C-MYC, which could be markedly blocked by JQ1 treatment. In conclusion, our findings revealed that the aberrant expression of BRD4 in thyroid cancer is possibly involved in tumor progression, and JQ1 is potentially an effective chemotherapeutic agent against human thyroid cancer. © 2015 Elsevier Inc. All rights reserved. Source