Experimental study of ¹³¹I inhibitory effect on hepatocellular carcinoma HepG2 cells induced by transferring saRNA-mediated NIS gene

Objective: To explore the feasibility of radionuclide imaging and treatment of Hepatocellular carcinoma induced by transferring small activating RNA (saRNA) mediated sodium iodide symporter (NIS) gene. Methods: Three saRNA sequences for NIS gene were designed and synthesized. The saRNAs were transfected into hepatoma HepG2 cells by using Lipofectamin^TM 2000 as the carrier. The NIS protein expression levels were determined by Western blotting analysis after 72 h. In vitro uptake and efflux of ¹²⁵I, proliferation inhibition of ¹³¹I on HepG2 Cells induced by transferring saRNA-mediated NIS gene were carried out. Results: The saRNA up-regulated the NIS gene expression levels, and the saRNA482 sequences up-regulated NIS with the highest expression level. The NIS expression levels reached its peak at 72 h after transfection and maintained more than 10 days. There was significantly difference on ¹²⁵I uptake between transfected cells and non-transfected cells, and the highest uptake of iodine in transfected cells was 64 times higher compared with control cells. Compared with control cells, the growth inhibition rates of ¹³¹I on NIS transfected HepG2 cells was 60.7%. Conclusion: The saRNA could upregulate the NIS express levels on hepatocellular carcinoma HepG2 cells and enhance its uptake for radio-iodine. The saRNA-mediated transfer of NIS gene into HepG2 cells might have potential for ¹³¹I targeted radiotherapy of hepatocellular carcinoma. (authors)