1306 KB13 KB199220251997Auersperg, MarijaČemažar, MajaSerša, Gregorletnik:31številka:4str. 364-367ISSN:1318-2099COBISSID:7834841URN:URN:NBN:SI:doc-9948LUA2enCroatian Medical Association - Croatian Society of RadiologySlovenian Medical Society - Section of RadiologyRadiology and oncology (Ljubljana)fiziologijaposkusirak (medicina)sarkomzdravljenjeVinblastine increases antitumor effectiveness of bleomycin|In our previous vinblastine (VELBE) was shown to increase the plasma membrane fluidity. This effect of VELBE might be expolited for better transport of drugs through the plasma membrane. Bleomycin (BLM) is a highly cytotoxic drug when present inside the cells but has a hampered transport through the plasma membrane. The aim of the present study was to determine whether pretreatment with VELBE can increase the effect of BLM on intraperitoneal SA-1 tumors in mice. BLM and VELBE were used as single agents or in various combinations, i.e. VELBE and BLM injected simultanously, BLM injected 24 h before VELBE or VELBE injected 24 h before BLM. Mice survival was the end-point used for determining the effect of this combined treatments. VELBE and BLM as a single treatment significantly prolonged median survival time of study animals compared to controls. Furthermore, when VELBE and BLM were combined, all threetested combinations were more effective than VELBE or BLM as single treatments. The effect on animal survival was equal when VELBE was given 24 h after or simultanously with BLM. The longest survival, however was obtained when VELBE was injected 24 h before BLM. From these results we can conclude that the underlying mechanisms for more than additive effect of VELBE and BLM when VELBE was given 24 h before BLM could be attributed to an increased membrane fluidity, possibly in combination with a cell kinetic effectV naši predhodni študiji smo ugotovili, da vinblastin poveča fluidnost plazemske membrane. S tem lahko povečamo vnos bleomcina, ki slabo prehaja preko plazemske membrane, a je zelo citotoksičen, če je prisoten v celici. Namen naše raziskave je bil na mišjih intraperitonealnih SA-1 tumorjih določiti, ali njiciranje vinblastina pred bleomicinom poveča učinkovitost bleomicina. Mišim smo injicirali samo vinblastin, samo bleomicin, vinblastin in bleomicin skupaj v različnih kombinacijah: vinblastin in bleomicin injicirana sočasno, bleomicin injiciran 24 h pred vinblastinom in vinblastin injiciran 24 h pred bleomicinom. Učinkovitost terapije smo ugotavljali s preživetjem živali. Zdravljenje z vinblastinom in bleomicinom je statistično značilno podaljšalo preživetje živali glede na kontrolno skupino. Vse tri kombinacije vinblastina in bleomicina so bile bolj učinkovite kot zdralvjenje samo z enim kemoterapevtikom. Učinek terapije je bil enak, če smo sočasno injicirali vinblastin in bleomicin, ali če smo injicirali bleomicin 24 h pred vinblastinom. Najdaljše preživetje živali pa smo dobili, če smo injicirali vinblastin 24 h pred bleomicinom. Glede na naše rezultate lahko predpostavljamo, da sta za dobljeni učinek terapije odgovorna dva mehanizma delovanja vinblastina: povečanje fluidnosti membrane in vejretno celično kinetični efektTEXTznanstveno časopisjejournalsSlovenian National E-content AggregatorNational and University Library of SloveniaOnkološki inštitut Ljubljana