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Background and Aim: Epstein - Barr virus (EBV)-encoded LMP1 is suggested to have an important role in the pathogenesis and development of nasopharyngeal carcinoma (NPC). Our previous study showed that As2O3 exhibited growth inhibition of NPC in animal model. Here, we further explore whether LMP1 is involved in As2O3 anticancer effects in NPC cell line., Methods: Both the stable expressing LMP1 cell line HNE1-LMP1 and its parental cell line HNE1 without LMP1 expression were used as in vitro models to assess arsenic trioxide effect. Both cell lines were treated with As2O3 for 72 h. The median inhibition concentration (IC50) was assessed by the MTT assay. Apoptosis was observed by phase-contrast microscopy and TUNEL staining. The alteration of telomere lengths was detected by Southern blotting., Results: IC50 for As2O3 in HNE1-LMP1 cells and HNE1 cells was 2.22 and 5.09 micromol/L, respectively. After exposure to 2 and 4 micromol/L As2O3 for 72 h, the apoptotic index in HNE1-LMP1 was 26.27 -/+ 1.3 and 49.13 -/+ 1.4%, respectively. On the contrary, in HNE1 cells the apoptotic index was 12.6 -/+ 0.9 and 33.20 -/+ 1.3%, respectively. As compared with parental cell line HNE1, HNE1-LMP1 cells were more sensitive to growth inhibition and apoptosis (p < 0.001). The elongation of telomere length was also found in HNE1-LMP1 cells. Meanwhile, longer telomeres in HNE1-LMP1 cells failed to maintain telomere stabilization, instead, it prone to be shortened when exposure to As2O3, as comparing with HNE1 cells., Conclusion: LMP1 plays important role in enhancing NPC cell response to As2O3. The elongation of telomere length induced by LMP1 may contribute to the mechanisms of As2O3 sensitivity.

DAP kinases are a family of serine/threonine kinases known to regulate intrinsic apoptotic processes. DAP-related apoptotic kinase-2 (DRAK2) is highly expressed in lymphoid organs, with differential expression during thymocyte development. Low levels of transcript were observed in CD4/CD8 double-positive (DP) and double-negative populations, whereas single-positive thymocytes possessed elevated levels. Ex vivo stimulation of DP thymocytes with phorbol myristate acetate or antibodies that activate the TCR complex led to the accumulation of DRAK2 in a protein kinase C- and MAP Kinase-dependent fashion. Although DAP kinase family members are thought to potentiate apoptosis, ectopic expression of DRAK2 using retroviral transduction of primary T cells and NIH3T3 fibroblasts failed to decrease rates of survival, suggesting that DRAK2 expression is not sufficient to promote apoptosis. Rather, our results demonstrate that DRAK2 is a primary response gene activated by TCR stimulation in DP thymocytes. Further, we observed that DRAK2 controlled the threshold for calcium signaling in the thymus since positively selected Drak2-deficient thymocytes displayed a reduced requirement for TCR cross-linking. These findings are consistent with a role for DRAK2 in thymocyte selection and lymphoid maturation, and demonstrate that DRAK2 transduces non-apoptotic signals during thymocyte differentiation.