Sodium iodide symporter/radioactive iodine system has more efficient antitumor effect in three-dimensional spheroids

Area of Science:

• Oncology
• Molecular Biology
• Radiotherapy

Background:

• The sodium iodide symporter (NIS) facilitates iodide uptake into thyroid cells.
• NIS gene expression in tumor cells offers a potential cancer treatment strategy.
• Previous studies showed NIS-mediated 131I killing in monolayer tumor cells, but lacked 3D tumor representation.

Purpose of the Study:

• To evaluate the efficacy of NIS gene therapy in a 3D multicellular tumor spheroid model.
• To assess radioisotope (131I) uptake and killing effect in NIS-transduced prostate cancer cells.
• To establish a more relevant in vitro model bridging cell cultures and animal studies.

Main Methods:

• Rat NIS gene was introduced into DU145 prostate cancer cells using a retroviral vector.
• Multicellular tumor spheroids were generated using the liquid-overlay technique.
• 125I uptake and 131I-induced cell killing were assessed in monolayer and spheroid cultures.

Main Results:

• NIS-expressing DU145 cells showed 40-50 fold greater 125I uptake than control cells.
• 131I treatment resulted in 50-70% cell killing in NIS-expressing monolayer cultures.
• Complete tumor spheroid death was observed with 131I in DU145-NIS cells.

Conclusions:

• NIS gene therapy demonstrates significant anti-tumor efficacy in a 3D multicellular spheroid model.
• This 3D spheroid model provides a valuable preclinical assessment tool for radioisotope-based gene therapy.
• NIS gene therapy holds promise for treating prostate cancer and other malignancies.