Efficiency and mechanism of antitumor activity of cardiolipin-like lipid/thymidine kinase gene HSV-tklipoplexes in the presence of gancyclovir

Abstract

The herpes simplex virus thymidine kinase/gancyclovir(HSV-tk/GCV) system is studied as cytotoxic lipoplex basedon cardiolipin-like dicationic lipid CDL-I. It is proposed to beused as nonviral gene transfer system in cancer gene therapyprotocols. Аn efficient transfection of MCF7 and HEC293 celllines with this lipoplex was earlier demonstrated. Non-viralsystem based on the CDL-I/HSV-tk lipoplex and ganciclovirtreatment causes efficiently death of tumor cells with aninvolvement of apoptosis key stages. It was proved thatdepolarization of mitochondrial membrane and increased levelof NF-kB transcription factor take place as a response to CDL-I/ HSV-tk lipoplex action followed by gancyclovir treatment. Itsuggests an early involvement of apoptosis mitochondrial wayto an action of this certain «suicide» system, delivered usingdicationic lipid.

Keywords

cancer gene therapy / apoptosis / dicationic lipids / non-viral of gene transfer systems / «suicide» herpes simplex virus thymidine kinase gene system / NF-kB transcription factor

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