thapsigargin and oblimersen

thapsigargin has been researched along with oblimersen* in 1 studies

Other Studies

1 other study(ies) available for thapsigargin and oblimersen

Article	Year
Relative Bcl-2 independence of drug-induced cytotoxicity and resistance in 518A2 melanoma cells. Clinical cancer research : an official journal of the American Association for Cancer Research, 2004, Dec-15, Volume: 10, Issue:24 Inhibition of the function of Bcl-2 protein has been postulated to sensitize cells to cytotoxic chemotherapy. G3139 (Genasense) is a phosphorothioate anti-Bcl-2 antisense oligonucleotide, but its mechanism of action is uncertain. The aim of the present work is to investigate inhibition of Bcl-2 expression in 518A2 melanoma cells, the cell line on which recent phase II and phase III clinical trials employing this agent were based.. We down-regulated the expression of Bcl-2 protein by two different strategies in these cells: one employing G3139 and controls, and the other using a small interfering RNA approach. Cell viability after treatment with oligonucleotides or small interfering RNA and cytotoxic agents including gemcitibine, DDP, docetaxel, and thapsigargin was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. A 518A2 melanoma cell line stably overexpressing Bcl-2 protein was constructed and treated with either these cytotoxic agents or G3139.. The cytotoxic effects of either G3139 or small interfering RNA treatment of 518A2 melanoma cells are Bcl-2 independent. In addition, in the Bcl-2-overexpressing cells, only a modest increment in chemoresistance was observed, and treatment with G3139 not only did not down-regulate Bcl-2 expression but produced essentially identical toxicity as was observed in the wild-type or mock-transfected cells.. Our results suggest that the mechanism whereby G3139 produces drug-induced cytotoxicity in the 518A2 melanoma line is not dependent on levels of Bcl-2. These findings emphasize the nonsequence specific effects of this phosphorothioate oligonucleotide and call into question the validity of Bcl-2 as a target in this cell line. Topics: Antineoplastic Agents; Apoptosis; Cisplatin; Deoxycytidine; Docetaxel; Down-Regulation; Drug Resistance, Neoplasm; Enzyme Inhibitors; Gemcitabine; Humans; Melanoma; Oligonucleotides, Antisense; Proto-Oncogene Proteins c-bcl-2; RNA, Messenger; RNA, Small Interfering; Skin Neoplasms; Taxoids; Thapsigargin; Thionucleotides; Tumor Cells, Cultured	2004

Article

Year

Relative Bcl-2 independence of drug-induced cytotoxicity and resistance in 518A2 melanoma cells.

Clinical cancer research : an official journal of the American Association for Cancer Research, 2004, Dec-15, Volume: 10, Issue:24

Inhibition of the function of Bcl-2 protein has been postulated to sensitize cells to cytotoxic chemotherapy. G3139 (Genasense) is a phosphorothioate anti-Bcl-2 antisense oligonucleotide, but its mechanism of action is uncertain. The aim of the present work is to investigate inhibition of Bcl-2 expression in 518A2 melanoma cells, the cell line on which recent phase II and phase III clinical trials employing this agent were based.. We down-regulated the expression of Bcl-2 protein by two different strategies in these cells: one employing G3139 and controls, and the other using a small interfering RNA approach. Cell viability after treatment with oligonucleotides or small interfering RNA and cytotoxic agents including gemcitibine, DDP, docetaxel, and thapsigargin was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. A 518A2 melanoma cell line stably overexpressing Bcl-2 protein was constructed and treated with either these cytotoxic agents or G3139.. The cytotoxic effects of either G3139 or small interfering RNA treatment of 518A2 melanoma cells are Bcl-2 independent. In addition, in the Bcl-2-overexpressing cells, only a modest increment in chemoresistance was observed, and treatment with G3139 not only did not down-regulate Bcl-2 expression but produced essentially identical toxicity as was observed in the wild-type or mock-transfected cells.. Our results suggest that the mechanism whereby G3139 produces drug-induced cytotoxicity in the 518A2 melanoma line is not dependent on levels of Bcl-2. These findings emphasize the nonsequence specific effects of this phosphorothioate oligonucleotide and call into question the validity of Bcl-2 as a target in this cell line.

Topics: Antineoplastic Agents; Apoptosis; Cisplatin; Deoxycytidine; Docetaxel; Down-Regulation; Drug Resistance, Neoplasm; Enzyme Inhibitors; Gemcitabine; Humans; Melanoma; Oligonucleotides, Antisense; Proto-Oncogene Proteins c-bcl-2; RNA, Messenger; RNA, Small Interfering; Skin Neoplasms; Taxoids; Thapsigargin; Thionucleotides; Tumor Cells, Cultured

2004