Dihydroartemisinin suppresses the proliferation of Epstein-Barr virus-associated gastric carcinoma cells via downregulation of latent membrane protein 2A

摘要

Treatment of recurrent and metastatic Epstein-Barr virus-associated gastric carcinoma (EBVaGC) remains a challenge, particularly in developing countries, due to lack of efficient screening programs. Latent membrane protein 2A (LMP2A) has been reported to serve an important function in the development of EBVaGC. In previous years dihydroartemisinin (DHA), traditionally used as an anti-malarial agent, has been demonstrated to inhibit tumor growth with low toxicity to normal cells. In the present study, the anti-tumor effect of DHA in EBVaGC was investigated. The MTT assay was used to compare the viability of untreated and DHA-treated EBVaGC GT-38 cells. Flow cytometry was applied to determine the percentage of GT-38 cells at each stage of the cell cycle. Reverse transcription-polymerase chain reaction and western blotting were used to determine the expression of the LMP2A gene. The effect of DHA treatment in vivo was evaluated in nude mice bearing GT-38 tumors. The results of the present study revealed that DHA-treated cells exhibited a time- and dose-dependent inhibition of viability. DHA significantly increased the apoptotic rate of GT-38 cells following treatment with 20 mu g/ml DHA for 48 h. DHA-treated GT-38 cells were blocked in the G(0)/G(1) phase, resulting in an accumulation of G(0)/G(1) phase cells and a significant decrease of G(2)/M phase cells. In vivo, the results of the present study revealed that DHA significantly inhibited the growth of GT-38 cell-transplanted tumors. The mRNA and protein levels of LMP2A were significantly downregulated in the DHA-treated group compared with the control group. The present data indicated that DHA inhibited cell growth and induced cell apoptosis of the EBVaGC GT-38 cell line via downregulation of LMP2A. DHA may therefore be a potential therapeutic candidate for the treatment of EBVaGC.