Latent membrane protein-1 of Epstein - Barr virus increases sensitivity to arsenic trioxide-induced apoptosis in nasopharyngeal carcinoma cell.
OBJECTIVE
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.


CONCLUSIONS
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.
Du
C W
CW
Laboratory of Cancer Research, Cancer Hospital, Shantou University Medical College, Shantou 515031, P.R. China.
Wen
B G
BG
Li
D R
DR
Lin
Y C
YC
Zheng
Y W
YW
Chen
L
L
Chen
J Y
JY
Lin
W
W
Wu
M Y
MY
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D015139:Blotting, Southern; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004854:Herpesvirus 4, Human / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000821:virology*; D010087:Oxides / Q000494:pharmacology*; D016615:Telomere; D014763:Viral Matrix Proteins / Q000378:metabolism*
D000970:Antineoplastic Agents; D001152:Arsenicals; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D010087:Oxides; D014763:Viral Matrix Proteins; D000077237:Arsenic Trioxide