NES1/KLK10 and hNIS gene therapy enhanced iodine-131 internal radiation in PC3 proliferation inhibition

Abstract

NES1 gene is thought to be a tumor-suppressor gene. Our previous study found that overexpression of NES1 gene in PC3 cell line could slow down the tumor proliferation rate, associated with a mild decrease in BCL-2 expression. The BCL-2 decrease could increase the sensitivity of radiotherapy to tumors. Thus, we supposed to have an “enhanced firepower” effect by combining overexpressed NES1 gene therapy and ¹³¹I radiation therapy uptake by overexpressed hNIS protein. We found a weak endogenous expression of hNIS protein in PC3 cells and demonstrated that the low expression of hNIS protein in PC3 cells might be the reason for the low iodine uptake. By overexpressing hNIS in PC3, the radioactive iodine uptake ability was significantly increased. Results of in vitro and in vivo tumor proliferation experiments and ¹⁸F-fluorothymidine (¹⁸F-FLT) micro-positron emission tomography/computed tomography (micro-PET/CT) imaging showed that the combined NES1 gene therapy and ¹³¹I radiation therapy mediated by overexpressed hNIS protein had the best tumor proliferative inhibition effect. Immunohistochemistry showed an obvious decrease of Ki-67 expression and the lowest BCL-2 expression. These data suggest that via inhibition of BCL-2 expression, overexpressed NES1 might enhance the effect of radiation therapy of ¹³¹I uptake in hNIS overexpressed PC3 cells.

Keywords

androgen-independent prostate cancer / normal epithelial cell-specific 1/kallikrein 10 / sodium/iodide symporter / radiation therapy / proliferation

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Acknowledgements

This study was financially supported by the foundation from the National Natural Science Foundation of China (Nos. 81501502 and 81570118), Scientific Research Project of Shanghai Municipal Commission of Health and Family Planning (No. 201740154), Multidisciplinary Cross-Project (Medical) of Shanghai Jiao Tong University (No. YG2017MS65), and the foundation of talent plan A for Guangci Excellent Youth of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (No. GCQN-2017-A12), and the National Key R&D Program of China (No. 2017YFA 0505200).

Compliance with ethics guidelines

Jiajia Hu, Wenbin Shen, Qian Qu, Xiaochun Fei, Ying Miao, Xinyun Huang, Jiajun Liu, Yingli Wu, and Biao Li declare no conflicts of interests. All institutional and national guidelines for the care and use of laboratory animals were followed.

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