The evidence of “Bystander” effect after bleomycin electrotransfer

Abstract

According to the World Health Organization, cancer is the cause of death of 9.6 million people in 2018. One of the options of cancer treatment is anticancer drug delivery or gene therapy. Therefore, intensive research is being done to obtain efficient and controlled transfer of drugs and genes to cells and tissues. Electrochemotherapy (ECT) is one of the possible options for novel cancer therapy that utilizes the method of electroporation. Electroporation occur once cells are stimulated with electric field at significant intensity, thus affected cell plasma membrane becomes temporarily permeable to various hydrophilic substances, such as the anticancer drug bleomycin (BLM). After BLM enters the cells its mechanism of action triggers the generation of, reactive oxygen species (ROS), resulting in multiple genomic DNA breaks hence leading to cell death. Similar phenomenon of ROS generation is being observed when radiotherapy performed. Then ionizing radiation is the cause of ROS generation in the target cells, that cause cell death. It is known that radiation-exposed cells when killed in the environment, secrete signaling molecules that affect adjacent cells but are not directly affected by ionizing radiation. This phenomenon is called the Bystander effect. Although the effect of Bystander is known in radiotherapy, it is unexplored in electrochemotherapy - there is no evidence that this phenomenon is possible during electrochemotherapy. Therefore, the aim of this study was to evaluate the effect of the Bystander effect on cell viability after irreversible electroporation and in vitro electrotransfer of the anticancer drug bleomycin. The study presented here is performed using CHO-K1 cells. The electrotransfer of the anticancer drug bleomycin is achieved using a single electrical pulse of 1400 V/cm amplitude and 100 μs duration. Irreversible electroporation is achieved using a single electrical pulse with an[...]