Experimental Evaluation of Gene Silencing As New Therapeutic Option in the Treatment of Gemcitabine-chemoresistant Non-small-cell Lung Cancer

Abstract

The evolution of technological and therapeutic applications of siRNA since the description of the interference process in 2006 has been extremely rapid and very productive. Currently, at least ten tumor entities and ten viral infections in which siRNA-based therapy might play an auspicious role have been described. Because of the very poor prognosis of NSCLC, we examined and proposed a new therapeutic alternative for the treatment of gemcitabine-resistant lung cancer via siRNA-specific silencing of six important molecules involved in lung carcinogenesis.Methods: One hundred thousand gemcitabine-chemoresistant A549 cell lines were cultured in a humidified atmosphere containing 5 % CO2 at 37°C and were transfected with specific siRNA targeting HIF1, HIF2, STAT3, SRF, E2F1 and Survivin. The relative expression of these molecules was examined via qRT-PCR and the viability of the chemoresistant cells after siRNA transfection was analyzed using a CASY system 72 hours after specific transfection.Results: The relative expression of the examined target molecules was suppressed by up to 73 % after specific transfection, and the CASY system demonstrated a concentration-dependent reduction in the viability of chemoresistant A549 cells of up to 61 %. Therefore the obtained results were significantly better in comparison to the control group.Conclusions: siRNA complexes may induce accurate suppression of various target molecules involved in lung tumor growth, in particular in gemcitabine- chemoresistant adenocarcinoma. Therefore, siRNA-based nanotechnology might represent a productive platform for the development of new chemotherapeutic agents for advanced stages of lung cancer in the context of a personalized multimodality regimen

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