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The Study Of Enhancing The Cytotoxicity Of Antitumor Drugs Through Electromagnetic Pulses

Posted on:2004-09-13Degree:MasterType:Thesis
Country:ChinaCandidate:G YangFull Text:PDF
GTID:2144360095452911Subject:Radio Physics
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Biological cell membrane is a lipoid liquid organism embedded spherical protein. The energy of electric field and thermal action has influence on transient pore's formation, and electric energy has relation with transmembrane potential on the surface of cells, also plays a decisive role in transient pore's formation. Generally the pole's radius is small, only allows small substances such as inorganic molecule to pass, and because of the existence of barrier layer to ion or charged molecule, it makes them pass indirectly. The permeability barrier is withheld when cell membrane is exposed to pulsed electric field, and now that electroporation is transient pore or permeable structure on cell membrane that will be last for 20 milliseconds and will be closed at the end because of the fluidity of cell membrane. So far some experiments proved that with electroporation caused by pulsed electric field of high intensity of 1400V/cm, anticancer drugs of different trans-membrane access can enhance their cytotoxicity to cancer cells exbgenously cultured 1~700 times compared with those of conventional therapy. We use LN-01Gene Pulser Transfection Apparatus in experiments to handle Hela cell, and the handled cells are found to have been electropored, meanwhile the best parameters of electric field on Hela cell have been found.When combined with anticancer drugs paclitaxel and then by cell flow sorter and the stains of typannan, electroporation causes survival rate of Hela cell to decrease obviously, and compared with single function of paclitaxel, death rate of cell increases. Under the condition of samedrug concentration, death rate of single function of paclitaxel is from 0.1% to 34%, death rate of combined function is from 23.5% to 65.9 % . According to these datas, we can say that the combination of anticancer drugs and electroporation is capable of causing higher cytotoxicity to cancer cells than anticancer drugs alone, death rate of cell groups with different drug concentrations are higher than paclitaxel alone. Prominence otherness analysis shows that the combination of paclitaxel and electromagnetic pulses is capable of causing higher death rate of Hela cell than paclitaxel alone obviously, and the otherness is prominent (P<0. 05)Cyclophosphamide is delivered into Hela cell by electroporation. Apoptosis rate and death rate of cell increase severely, and the cytotoxicity at low pose is so tense as at high pose. Compared with Cyclophosphamide alone, under the condition of same drug concentration, survival rate of combined function decreases 57%, 44.3 %, 20.1% respectively, apoptosis rate increases 32.2%, 30.1%, 30.8 % respectively. By the staining of acridine orange, the quintessential apoptosis cells with nuclear condensation and flaw have been founded. Furthermore, life rate of cell has nothing to do with the concentration of antitumor drugs when the concentration reaches some degree. It says that survival rate at low pose is equal to that at high pose. In definite concentration range of drugs, survival rate of cell handled by electric field has relation with the concentration of drugs in evidence. Compared the electroporation group handled only by electric field with the contrast group, survival rate of cell is low.Chromosome is the carrier of germ plasm. When combined with electric field, SFL can cause higher chromosome aberration rate and micronucleus rate than it works alone. It shows that SFL damages DNA severely. Under the condition of same drug concentration, chromosome aberration rate of combined function increases 1. 34%, 4. 37%, 6. 7%. 11. 6% respectively, micronucleus rate increases 0.3.3%, 1. 66%, 4. 34%, 5.03% respectively. According to statistics analysis, the obvious otherness of chromosome aberration rate and micronucleus rate between combined function and function alone exists (P <0. 05) . It can be concluded that electric function can enhance the cytotoxicity of SFL to fetal cord blood lymphocytes.
Keywords/Search Tags:Electroporation, Antitumor drug, Cytotoxicity, Apoptosis
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