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Study & Mechanism Analysis Of Improving Anticancer Drug Effect Due To Cell Membrane Electroporation Of Electric Pulses Of High-Intensity

Posted on:2003-12-17Degree:MasterType:Thesis
Country:ChinaCandidate:J R SunFull Text:PDF
GTID:2144360065460749Subject:Zoology
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Electroporation is believed to be the transient creation of micropores in lipid bilayer of cell membrane due to the effects of electric pulses. It is a biophysics process,which can increase the permeation and conductance of cell membrane. This increase allows many molecules,such as aqueous affinity molecules,virosomes,DNA,proteins and dye granules,etc,which can not pass through cell membrane in normal conditions,to go through cell membrane.Recently,many scientists have taken advantage of characteristics of electroporation,combined with morden medicine,to develop new anticancer methods.Because of the promising application of electroporation in curing cancer,our research program has used the high-intensity electric pulses produced by LN-101 Gene Pulser Transfection Apparatus,combined with several anticancer drugs in a series of experiments. The results showed curing cancer by electroporation was a feasible way.My thesis includes four sections. In the first section,that electroporation can be induced on chick's erythrocytes by high-intensity electric pulses was investigated. The most direct proof of morphology was acquired. The mechanism of electroporation has been preliminarily studied. In the second section,that electroporation can enhance the cytotoxicity of some anticancer drugs was researched. The methods,such as MTT colorimetry,chromosome aberration and micronucleus have been used in this section. The results implied that electroporation can increase the cytotoxicity remarkably. In the third section,the effects of high-intensity electric pulses on the growth of HeLa cells were studied. The results showed that the high-intensity electric pulses can induce apoptosis in HeLa cells. The following experimental methods wereused in this section:fluorescence staining,DNA Ladder assay,flow cytometry,and so on. In the fourth section,an animal tumor model has been constructed. KM mouse and S-180 sarcoma cell have been chosen as researching targets and the cyclophosphamide was chosen as the anticancer drug. The results showed that the experimental group of electric field combined with drugs has the best effect on cancer,compared with the control group.From the above research,we know that electroporation can be induced in cancer cell membrane by the effects of high-intensity electric pulses,which can make anticancer drugs pass through cancer cell membrane and take effect to the largest degree.. At the same time,high-intensity electric pulses can induce apoptosis,making cancer cell go into the programmed cell death. In addition,electric field can inhibit the formation of vas capillaries,which were largely produced during the formation of cancer tissues to take nutrition from blood for those tissues. As a result,high-intensity electric pulses can decrease the supply of nutrition for cancer cells,and slow the speed of metabolism of them. In conclusion,electric field has inhibited the growth of cancer.At present,the tendency of exploting the electroporation lies in electrotransfection,electroinsertion,electrofusion,electrotransformation and constructing genebank,and so on.All of these applications base on the fact that the membrane permeability barrier can be temporarily suppressed when cells are subjected to transient high-intensity pulsed electric fields,so particles can be transferred into cells to take advantage of the traits of the free exchange of molecules between the cell interior and exterior.As time going on,the study on electroporation will be more and more expanding and profound. We believe the research and application of high-intensity electric pulses combined with anticancer drugs will have a full development.
Keywords/Search Tags:Electroporation, High-intensity electric pulse, ECT, Anticancer drug, Apoptosis
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