Search academic texts

Information × Registration Number 0217U000855, 0113U000141 , R & D reports Title The study of molecular mechanisms in response of tumor cells to the action of enzymotherapy based on starvation for arginine popup.stage_title Head Stasyk Oleh Volodymyrovych, Кандидат біологічних наук Registration Date 10-03-2017 Organization Institute of cell biology, National Academy of Sciences of Ukraine popup.description2 The results of clinical trials of anticancer enzymotherapy based on recombinant arginine-degrading enzymes indicate the need for its further improvement, including the development of more effective combinational approaches. The necessary but not sufficient condition of tumor cell sensitivity to therapy in vivo is damaged utilization of the anabolic arginine precursor citrulline, which is mediated by the enzyme argininosuccinate synthetase (ASS). However, our previous studies have established that the status of arginine anabolic enzymes, including ASS, does not determine the sensitivity of tumor cells to this treatment in vitro. From the published data it is also known that reducing expression of ASS in some cases probably correlates with increased metastatic potential of tumor cells. The study to determine the influence of ASS status on the physiology of cultured human glioma cells, including their metastatic potential, was conducted in the department of cell signaling. It was established that the ASS protein level in all studied human neuroblastoma and glioma cell lines does not always correlate with the ability of cells to proliferate in the medium with citrulline. Using shRNA silencing approach clones of human glioma cell line U251 with stable ASS gene downregulation were selected. The vector for ASS expression in mammalian cells was constructed to obtain a stably transfected U251 cell line with elevated ASS. It was shown for the first time that ASS silencing increased clonogenic homotypic potential and cell adhesion of human glioma cells U251 in vitro. We also established that lack of the expression of ASS had no apparent effect on cell migration properties in U251, however, it increased their invasiveness. Also, a producer of the ASS recombinant human protein based on Esherichia coli was obtained and a protein purification scheme was developed aimed at further research on ASS effective inhibitors, suitable for in vivo applications. Product Description popup.authors Ігуменцева Н.І. Барська М.Л. Бобак Я.П. Винницька Б.О. Вовк О.І. Воробець З.Д. Данилейченко В.В. Денега І.О. Кавалець Б.Б. Карацай О.В. Курліщук Ю.В. Линів Л.С. Переверзєва Г.Г. Ржепецький Ю.А. Сенчук О.Ю. Сибірна Н.О. Стасик О.Г. Чень О.І. Чернишук С.В. Шуваєва Г.Ю. popup.nrat_date 2020-04-02 Close