Arsenic trioxide reduces the invasive and metastatic properties of nasopharyngeal carcinoma cells in vitro

Abstract

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 (As 2 O 3 ) 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 µM As 2 O 3 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 As 2 O 3 -treated HNE1-LMP1 cells. iii) The reduction of MMP-9 was found in As 2 O 3 -treated groups, more evident in HNE1-LMP1 cells. Thus, we conclude that As 2 O 3 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 As 2 O 3 .

Tumor growth inhibition of metastatic nasopharyngeal carcinoma cell lines by low dose of arsenic trioxide via alteration of cell cycle progression and induction of apoptosis

“…Subsequently, the NPC cells entered the apoptotic pathway after accumulation of cells in the G0/G1 and G2/M phases and lost their invasive ability. 20,50 The present finding was consistent with the previous report 20,21 and showed that the levels of LMP-1 and Bcl-2 in ATO-treated BM-1 and BM-2 cells decreased. This effect may contribute to induction of apoptosis and inhibition of tumor growth.…”

p37 from Mycoplasma hyorhinis promotes cancer cell invasiveness and metastasis through activation of MMP-2 and followed by phosphorylation of EGFR

“…According to the previous method (22), the bottom chamber was filled with 800 AL medium containing 10% FCS and 2% bovine serum albumin as chemoattractant. Cells resuspended in serum-free medium, containing p37 with inhibitors or DMSO, were carefully transferred onto the top chamber of each Transwell apparatus at a density of 10 6 cells/mL (100 AL/chamber).…”

Embelin prevents LMP1-induced TRAIL resistance via inhibition of XIAP in nasopharyngeal carcinoma cells

“…Latent membrane protein 1 (LMP1) is the principle oncogene of EBV (15), and LMP1 immortalizes and transforms cells by controlling the signaling pathways that block apoptosis and stimulate cell proliferation (16). LMP1 induces chemoresistance and promotes cell survival in NPC (17,18).…”