tailieunhanh - báo cáo hóa học:" Electroporation increases antitumoral efficacy of the bcl-2 antisense G3139 and chemotherapy in a human melanoma xenograft"

Tuyển tập các báo cáo nghiên cứu về hóa học được đăng trên tạp chí sinh học đề tài : Electroporation increases antitumoral efficacy of the bcl-2 antisense G3139 and chemotherapy in a human melanoma xenograft | Spugnini et al. Journal of Translational Medicine 2011 9 125 http content 9 1 125 JOURNAL OF TRANSLATIONAL MEDICINE RESEARCH Open Access Electroporation increases antitumoral efficacy of the bcl-2 antisense G3139 and chemotherapy in a human melanoma xenograft 1 2 2 2 2 3 Enrico P Spugnini Annamaria Biroccio Roberta De Mori Marco Scarsella Carmen DAngelo Alfonso Baldi and Carlo Leonetti 2 Abstract Background Nucleic acids designed to modulate the expression of target proteins remain a promising therapeutic strategy in several diseases including cancer. However clinical success is limited by the lack of efficient intracellular delivery. In this study we evaluated whether electroporation could increase the delivery of antisense oligodeoxynucleotides against bcl-2 G3139 as well as the efficacy of combination chemotherapy in human melanoma xenografts. Methods Melanoma-bearing nude mice were treated . with G3139 and or cisplatin DDP followed by the application of trains of electric pulses to tumors. Western blot immunohistochemistry and real-time PCR were performed to analyze protein and mRNA expression. The effect of electroporation on muscles was determined by histology while tumor apoptosis and the proliferation index were analyzed by immunohistochemistry. Antisense oligodeoxynucleotides tumor accumulation was measured by FACS and confocal microscopy. Results The G3139 Electroporation combined therapy produced a significant inhibition of tumor growth TWI more than 50 accompanied by a marked tumor re-growth delay TRD about 20 days . The efficacy of this treatment was due to the higher G3139 uptake in tumor cells which led to a marked down-regulation of bcl-2 protein expression. Moreover the G3139 EP combination treatment resulted in an enhanced apoptotic index and a decreased proliferation rate of tumors. Finally an increased tumor response was observed after treatment with the triple combination G3139 DDP EP showing a TWI of about 75