Therapeutic effects of adenovirus‑mediated CD and NIS expression combined with Na131I/5‑FC on human thyroid cancer

Abstract

Abstract. Thyroid cancer is the most common type of malignant endocrine tumor diagnosed. Previous studies have indicated that gene therapy is the most promising and effective therapeutic method for thyroid cancer. Therefore, in the present study, Na 131 I/5-fluorocytosine (5-FC) treatment was combined with cytosine deaminase (CD, encoded by the CDA gene) and sodium iodide symporter (NIS, encoded by the SLC5A5 gene) to act together as a therapeutic tool for thyroid cancer. The present study explored the combined cytotoxic effects of adenovirus-mediated CD and NIS under the control of the progression elevated gene-3 (PEG-3) promoter (Ad-PEG-3-CD-NIS) with Na 131 I/5-FC against the human thyroid cancer TT cell line in vitro. The PEG-3 fragment was obtained by polymerase chain reaction (PCR) using rat genomic DNA as the template, and then Ad-PEG-3-CDA-SLC5A5 was constructed using XbaI. TT cells were transfected by recombinant adenovirus. The method of reverse transcription-quantitative PCR was performed to test the expression of CD and NIS at the level of transcription. The morphological change was assessed by fluorescence microscopy and investigated by western blot analysis. An MTT assay was used to determine the number of living cells inhibited by single or combination therapies on TT cells. The results indicated that the PEG-3 was successfully cloned, and was also positively regulated in 293 cells. CDA and SLC5A5 genes were highly expressed in TT cells. Na 131 I combined with 5-FC significantly decreased the human thyroid cancer cells. In conclusion, combination therapy of Ad-PEG3-CDA-SLC5A5 and Na 131 I/5-FC induces significantly more apoptotic characteristics than either single treatment with Ad-PEG-3-CDA-SLC5A5 or Na 131 I/5-FC, and low doses of Ad-PEG-3-CDA-SLC5A5 enhanced the cytotoxic effects.

Circadian Genes MBOAT2/CDA/LPCAT2/B4GALT5 in the Metabolic Pathway Serve as New Biomarkers of PACA Prognosis and Immune Infiltration

“…The efficacy of CDA is variable; cytarabine, for example, has a higher efficacy in the treatment of acute myeloid leukemia, and gemcitabine has a higher efficacy in the treatment of breast cancer. CDA is related to drug chemotherapy and can also be used as a method to mediate the treatment of endocrine tumors in thyroid cancer [ 21 , 22 , 23 , 24 , 25 ]. However, CDA polymorphisms are barely associated with lung cancer [ 26 ].…”

Systemic delivery and SPECT/CT in vivo imaging of 125I-labelled oncolytic adenoviral mutants in models of pancreatic cancer

“…In contrast to genetically engineered viruses such as those that express the human Na/I symporter (hNIS), requiring the modification of each mutant and delivery of 125 I or 131 I at high doses ( e . g. 37,38 ), our simpler direct labeling method does not require any genetic engineering and therefore enables for quicker results. Similarly, viral mutants expressing EGFP or RFP fluorescent proteins or Luciferase enzymes also require genetic modifications and the methods used for detection are generally less sensitive.…”