In vitro and in vivo, 188Re significantly reduced the survival of HeLa-TERTNIS cells and inhibited the growth of HeLa-TERTNIS xenografts, respectively. Further, 188Re uptake and accumulation were significantly higher in HeLa-TERTNIS cells and xenografts than HeLa cells and xenografts. Quantitative PCR and western blotting confirmed that HeLa-TERTNIS cells expressed high levels of NIS mRNA and protein, respectively. eGFP expression controlled by the hTERT promoter was substantially higher in the tumor cells than normal cells. The therapeutic effects of 188Re were assessed over 21 days on the basis of tumor volume and the immunohistochemical findings of excised tumors. HeLa and HeLa-TERTNIS tumor xenografts were transplanted in nude mice, and in vivo 188Re distribution was measured using micro-SPECT/CT imaging. A cervical cancer HeLa cell line stably expressing NIS (HeLa-TERTNIS) was created and examined in a similar way. To determine the tumor-specific transcriptional activity of the hTERT promoter, the eGFP-expressing vector was stably transfected into tumor cells and normal cells.
We constructed two recombinant lentiviral vectors expressing enhanced green fluorescent protein (eGFP) or the NIS gene driven by the hTERT promoter. We examined the therapeutic effects of rhenium-188 (188Re) in a cervical cancer xenograft model expressing the NIS gene under the control of the tumor-specific human telomerase reverse transcriptase (hTERT) promoter. The sodium iodine symporter (NIS) gene has often been used in cancer therapy and imaging. These results indicate that the expression of NIS under the control of the survivin promoter may be used to achieve cancer-specific expression of NIS in A549 lung cancer cells, which may be a possible strategy for targeted cancer gene therapy.Īlthough survival rates for cervical cancer have improved, they need further improvement in patients with distant metastases. Moreover, the combination of Ad-Sur-NIS transfection and 131I radionuclide therapy suppressed tumor growth and prolonged survival. In vivo, the Ad-Sur-NIS-transfected tumors also exhibited significant radioiodine accumulation (16.96☒.99% ID/g at 2 h post-injection) with an effective half-life of 7.72☐.61 h. The clonogenic assays demonstrated that the Ad-Sur-NIS-transfected A549 cells were selectively killed by exposure to 131I. However, no significant iodide uptake was observed in the normal human DPF cells following adenovirus transfection. In vitro, the A549 cells exhibited perchlorate-sensitive iodide uptake following transfection with the Ad-Sur-NIS adenovirus that was 54-fold greater than that of the cells transfected with the Ad-Sur-GFP negative control. Additionally, the adenovirus was intratumorally injected into tumor-bearing mice for in vivo transfection biodistribution studies and scintigraphic imaging were then performed. NIS gene expression was evaluated using 125I uptake and efflux assays. The recombinant adenovirus which contains the NIS gene and is driven by the survivin promoter, was name Ad-Sur-NIS, and transfected into A549 lung cancer cells and human normal dental pulp fibroblast DPF cells. This study aimed to develop a gene expression targeting method specific for the imaging and therapy of non-small cell lung cancer A549 cells using an adenovirus vector containing the human sodium iodide symporter (NIS) gene driven by the survivin promoter.
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