TAILIEUCHUNG - Báo cáo y học: "RNA interference of argininosuccinate synthetase restores sensitivity to recombinant arginine deiminase (rADI) in resistant cancer cells"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: RNA interference of argininosuccinate synthetase restores sensitivity to recombinant arginine deiminase (rADI) in resistant cancer cells | Wu et al. Journal of Biomedical Science 2011 18 25 http content 18 1 25 NSC The cost of publication in Journal of Biomedical Science Is borne by the National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access RNA interference of argininosuccinate synthetase restores sensitivity to recombinant arginine deiminase rADI in resistant cancer cells Fe-Lin Lin Wu1 2 3 Yu-Fen Liang 1 Yuan-Chen Chang1 Hao-Hsin Yo1 Ming-Feng Wei4 and Li-Jiuan Shen1 2 3 Abstract Background Sensitivity of cancer cells to recombinant arginine deiminase rADI depends on expression of argininosuccinate synthetase AS a rate-limiting enzyme in synthesis of arginine from citrulline. To understand the efficiency of RNA interfering of AS in sensitizing the resistant cancer cells to rADI the down regulation of AS transiently and permanently were performed in vitro respectively. Methods We studied the use of down-regulation of this enzyme by RNA interference in three human cancer cell lines A375 HeLa and MCF-7 as a way to restore sensitivity to rADI in resistant cells. The expression of AS at levels of mRNA and protein was determined to understand the effect of RNA interference. Cell viability cell cycle and possible mechanism of the restore sensitivity of AS RNA interference in rADI treated cancer cells were evaluated. Results AS DNA was present in all cancer cell lines studied however the expression of this enzyme at the mRNA and protein level was different. In two rADI-resistant cell lines one with endogenous AS expression MCF-7 cells and one with induced AS expression HeLa cells AS small interference RNA siRNA inhibited 37-46 of the expression of AS in MCF-7 cells. ASsiRNA did not affect cell viability in MCF-7 which may be due to the certain amount of residual AS protein. In contrast ASsiRNA down-regulated almost all AS expression in HeLa cells and caused cell death after rADI treatment. Permanently down-regulated AS expression by short hairpin RNA shRNA made

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