文章基本信息

标题：Reporter PET Images Bortezomib Treatment-Mediated Suppression of Cancer Cell Proteasome Activity
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作者：Jin Hee Lee ; Kyung-Ho Jung ; Cung Hoa Thien Quach 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2018
卷号：8
期号：1
页码：12290
DOI：10.1038/s41598-018-29642-w
语种：English
出版社：Springer Nature
摘要：Proteasomal protein degradation is a promising target for cancer therapy. Here, we developed a positron emission tomography (PET) technique based on the sodium-iodide symporter (NIS) gene fused with the carboxyl-terminal of ornithine decarboxylase (cODC) that noninvasively images cancer cells with inhibited proteasome activity. A retroviral vector was constructed in which the murine cODC degron was fused to the human NIS gene (NIS-cODC). Transiently transduced CT26 and HT29 colon cancer cells and stably expressing CT26/NIS-cODC cells were prepared. In cancer cells transiently transduced with NIS-cODC, NIS expression and transport activity was low at baseline, but NIS protein and ¹²⁵I uptake was significantly increased by inhibition of proteasome activity with bortezomib. Stable CT26/NIS-cODC cells also showed increased cytosolic and membrane NIS by bortezomib, and four different stable clones displayed bortezomib dose-dependent stimulation of ¹²⁵I and ^99mTc-0₄⁻ uptake. Importantly, bortezomib dose-dependently suppressed survival of CT26/NIS-cODC clones in a manner that closely correlated to the magnitudes of ¹²⁵I and ^99mTc-0₄⁻ uptake. CT26/NIS-cODC tumors of bortezomib-treated mice demonstrated greater ¹²⁴I uptake on PET images and increased NIS expression on tissue staining compared to vehicle-injected animals. NIS-cODC PET imaging may allow noninvasive quantitative monitoring of proteasome activity in cancer cells treated with bortezomib.