Enhanced Tumor Cell Apoptosis Research Articles

Ectopic expression of the thyroperoxidase gene augments radioiodide uptake and retention mediated by the sodium iodide symporter in non-small cell lung cancer.

Radioiodide is an effective therapy for thyroid cancer. This treatment modality exploits the thyroid-specific expression of the sodium iodide symporter (NIS) gene, which allows rapid internalization of iodide into thyroid cells. To test whether a similar treatment strategy could be exploited in nonthyroid malignancies, we transfected non-small cell lung cancer (NSCLC) cell lines with the NIS gene. Although the expression of NIS allowed significant radioiodide uptake in the transfected NSCLC cell lines, rapid radioiodide efflux limited tumor cell killing. Because thyroperoxidase (TPO) catalyzes iodination of proteins and subsequently causes iodide retention within thyroid cells, we hypothesized that coexpression of both NIS and TPO genes would overcome this deficiency. Our results show that transfection of NSCLC cells with both human NIS and TPO genes resulted in an increase in radioiodide uptake and retention and enhanced tumor cell apoptosis. These findings suggest that single gene therapy with only the NIS gene may have limited efficacy because of rapid efflux of radioiodide. In contrast, the combination of NIS and TPO gene transfer, with resulting TPO-mediated organification and intracellular retention of radioiodide, may lead to more effective tumor cell death. Thus, TPO could be used as a therapeutic strategy to enhance the NIS-based radioiodide concentrator gene therapy for locally advanced lung cancer.

The role of mitomycin antibiotics in the chemotherapy of solid tumors

The conventional administration of Mitomycin C (MMC) in intravesical instillations has its limitations. In this study, MMC was loaded onto an in situ forming depot consisting of chitosan (CS), β-glycerophosphate (GP) and Fe3O4 magnetic nanoparticles (Fe3O4-MNPs) to improve its effects. The features and effects of this new drug delivery mode were investigated. The new drug delivery system (Fe3O4-MMC-CS/GP) exhibited superior sol-gel transformation and magnetism. Sustained release of MMC was observed both in vitro and in vivo, and the retention, which lasted for 72 h in the rat bladder, was further examined using frozen sections. The Cell-Counting Kit-8 (CCK-8) and flow cytometry assays revealed better anti-tumor activity of Fe3O4-MMC-CS/GP compared with the free MMC solution. Animal experiments showed that Fe3O4-MMC-CS/GP provided a favorable survival rate and inhibited the growth of bladder tumors. Moreover, this drug delivery system enhanced tumor cell apoptosis compared with the conventional route of MMC administration in rats.