Arsenic trioxide reduces the invasive and metastatic properties of nasopharyngeal carcinoma cells in vitro.
Nasopharyngeal carcinoma (NPC) is notorious for the metastases, which are in close association with Epstein-Barr virus-encoded latent membrane protein 1 (LMP1). Arsenic trioxide (As2O3) has been shown to induce apoptosis and differentiation in NPC xenografts. Then, can it repress the cancer cells' metastasis potential? To elucidate this issue, the present study was performed. LMP1-negative cell line HNE1 and LMP1-positive cell line HNE1-LMP1 were used as in vitro model. Cells (1 x 10(5)/mL) were cultured with or without 3 microM As2O3 for 48 h. Then the survival cells were collected to investigate their potential of colony formation, attachment, invasion, and migration. Both confocal immunofluorescence staining and Western blot were used to detect the changes of LMP1 expression. The changes of MMP-9 were examined by RT-PCR assay and Western blot. The results were as follow: i) the colony formation inhibition rate (75.41 +/- 3.9% in HNE1-LMP1 cells vs 37.89 +/- 4.9% in HNE1 cells), the rate of attachment (HNE1-LMP1 vs HNE1: 56.40 +/- 3.5 vs 65.87 +/- 5.9%), the invasion inhibitory rate (HNE1-LMP1 vs HNE1: 56.50 +/- 3.7 and 27.91 +/- 2.1%), and the migration inhibitory rate (HNE1-LMP1 vs HNE1: 48.70 +/- 3.9 vs 29.19 +/- 6.27%) were all significantly different between the two cell lines (P < 0.01). ii) LMP1 was down-regulated in As2O3-treated HNE1-LMP1 cells. iii) The reduction of MMP-9 was found in As2O3-treated groups, more evident in HNE1-LMP1 cells. Thus, we conclude that As2O3 can reduce metastasis potential of NPC cells, involving inhibition of MMP-9 expression. LMP1 were also reduced in this process and seemed to enhance anti-metastasis activity of As2O3.
Du
C W
CW
Laboratory of Cancer Research, Cancer Hospital, Shantou University Medical College, Guang Dong, PR, China.
Wen
B G
BG
Li
D R
DR
Peng
X
X
Hong
C Q
CQ
Chen
J Y
JY
Lin
Z Z
ZZ
Hong
X
X
Lin
Y C
YC
Xie
L X
LX
Wu
M Y
MY
Zhang
H
H
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects* / Q000235:genetics; D018613:Microscopy, Confocal; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology; D010087:Oxides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014763:Viral Matrix Proteins / Q000187:drug effects* / Q000235:genetics
D000970:Antineoplastic Agents; D001152:Arsenicals; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D010087:Oxides; D012333:RNA, Messenger; D014763:Viral Matrix Proteins; D020780:Matrix Metalloproteinase 9; D000077237:Arsenic Trioxide