Mobile website
Basic Research
Gamma-secretase inhibitor-induced B lymphoma cell apoptosis
- Article
- Figures
- Metrics
- Preview PDF
- Reference
- Related
- Cited by
- Materials
Abstract:
Objective: To investigate the effect of γ-secretase inhibitor (GSI) on proliferation and apoptosis of B lymphoma in vitro and in vivo. Methods: In experiments in vitro, Burkitt lymphoma (BL) Namalwa cells were treated with GSI at different concentrations. At different time points after treatment, cell viability and apoptosis were assessed by MTT assay and flow cytometry, respectively. Apoptosis-related proteins caspase-3 and caspase-9 and Notch signaling pathway proteins were assessed by Western blotting. In experiments in vivo, nude mice were injected with Namalwa cells. Mice that developed tumor lesions after xenograft implantation were treated with GSI or PBS. Tumor development was comparatively assessed in the two treatment groups. Results: GSI inhibited Namalwa cell proliferation in time- and dose-dependent manners; at 48 h and 72 h after treatment, the IC50 value was 2.14 μmol/L and 0.61 μmol/L, respectively. GSI also induced Namalwa cell apoptosis in a time-dependent manner; (17.71±1.87)% of Namalwa cells treated with GSI at 125 μmol/L but only 3.42±0.95 % of cells treated with PBS underwent apoptosis at 24 h (P<0.01), and these numbers (43.68±0.53)% and (4.65±0.8)%, respectively, at 48 (P<0.01). Contents of caspase-3 and caspase-9 and intracellular Notch proteins were decreased but activated caspase-9 protein content was increased in a time-dependent manner in Namalwa cells after GSI treatment. In tumor-bearing nude mice, GSI treatment for 13 days resulted in a significant decrease in the tumor volume as compared with the PBS control (2.199±0.183% vs 1.15±0.399%, P＜0.01). Correspondingly, a significantly higher rate of apoptosis was detected in tumors from GSI-treated animals (5.3±0.48)% than in PBS-treated animals (2.1±0.26) %(P<0.01). Conclusions: GSI can efficiently inhibit the proliferation and promote apoptosis of B lymphoma cells, at least through regulating caspase-3 and caspase-9 and Notch signaling pathway.
Keywords:
Project Supported:
Project supported by the National Natural Science Foundation for Young Scholars of China（No. 81101786），and the Six Top Talents Foundation of Jiangsu Province（No. 2011-ws-062）
Clc Number:
