Cell penetrating peptide of sodium-iodide symporter effect on the I-131 radiotherapy on thyroid cancer

Abstract

The aim of the present study was to clarify whether the cell penetrating peptide of sodium-iodide symporter (NIS) has an effect on the I-131 radiotherapy of thyroid cancer. Firstly, we combined the HIV-1 TAT peptide (a cell penetrating peptide, dTAT) and established a nanoparticle vector (dTAT NP) to study the delivery efficiency of this cell-penetrating strategy for tumor-targeted gene delivery. dTAT NP was transfected into cultured TPC-1 cells as a model to study the effects of I-131 radiotherapy on thyroid cancer. Reverse transcription-quantitative polymerase chain reaction and western blotting results showed that the mRNA and protein expression levels of NIS in the transfected TPC-1 cells were substantially higher than in the negative control cells. MTT and flow cytometric analyses demonstrated that the cell growth and apoptosis rates of the TPC-1 cells were significantly inhibited and activated, respectively, by treatment with dTAT NP. The results of DAPI staining showed that treatment with dTAT NP visibly increased the nuclear apoptosis rate of the TPC-1 cells. The effect of dTAT NP on TPC-1 cells was associated with the promotion of caspase-3 and downregulation of the PI3K/Akt signaling pathway. In summary, the present data provide a pre-clinical proof-of-concept for a novel gene delivery system that efficiently delivers NIS to the targeted cancer cells and presents a satisfactory efficacy. This approach may offer an effective strategy for improving thyroid cancer gene therapy.

Fluorescent magnetic submicronic polymer (FMSP) nanoparticles induce cell death in human colorectal carcinoma cells

“…The nuclear fragmentation and disintegration is a characteristic of apoptosis [42]. There are also several studies which have reported the use of DAPI as early indicator of apoptotic cell death [42][43][44][45]. We do not know the mechanism of action of FMSP-nanoparticles in eliciting cell death, the possibility of apoptotic pathways cannot be ruled.…”

“…The 12.5 m2/mL and 50 m0/mL dosages caused a significant nuclear condensation, fragmentation and disintegration. The nuclear fragmentation and disintegration is a characteristic of apoptosis [42]. There are also several studies which have reported the use of DAPI as early indicator of apoptotic cell death [42][43][44][45].…”

Evaluating the Natrium Iodide Symporter Expressions in Thyroid Tumors

“…Higher NIS expression is associated with higher uptake of 131 I by thyroid cell [18], [34]. Thyroid cells that do not respond to radioiodine can be lost NIS expression [15], [17], [23], [24]. The availability of specific polyclonal and monoclonal anti-hNIS antibodies has allowed the investigation of NIS protein expression levels in various thyroid tissues.…”

“…It resides in the thyroid in the basolateral membrane of epithelial cells and transports two cations of sodium (Na+) and one anion of iodide (I-) into the cells. This process is facilitated by an enzyme Na+/K+ ATPase [21], [22], [23].…”

“…Decreased NIS expression levels or diminished NIS targeting to thyroid cancer cells' plasma membrane lead to radioiodine-refractory disease. The main reason for impaired of 131 I uptake is defective of NIS expression [15], [17], [23], [24]. This study aims to analyze the NIS expression in thyroid tumors.…”